<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:5f0379f9-2273-49e0-a50e-d93977dcfc74,g:b69194c4-7d97-416f-b780-b42c93b0c555-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.supernus.com/role/ConsolidatedStatementsofEarnings" xlink:type="simple" xlink:href="supn-20241231.xsd#ConsolidatedStatementsofEarnings"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ConsolidatedStatementsofEarnings" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_bb51a070-72b3-45b7-828b-2f86b2063747" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_StatementTable_bb51a070-72b3-45b7-828b-2f86b2063747" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_938a7ebb-6172-4685-aa22-98d064d8e43b" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_bb51a070-72b3-45b7-828b-2f86b2063747" xlink:to="loc_srt_ProductOrServiceAxis_938a7ebb-6172-4685-aa22-98d064d8e43b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_938a7ebb-6172-4685-aa22-98d064d8e43b_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_938a7ebb-6172-4685-aa22-98d064d8e43b" xlink:to="loc_srt_ProductsAndServicesDomain_938a7ebb-6172-4685-aa22-98d064d8e43b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_537eadbb-8440-4869-9e48-ef327b3bb6ff" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_938a7ebb-6172-4685-aa22-98d064d8e43b" xlink:to="loc_srt_ProductsAndServicesDomain_537eadbb-8440-4869-9e48-ef327b3bb6ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_eb73821e-0b0f-4f92-9124-88f5ccc39166" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_537eadbb-8440-4869-9e48-ef327b3bb6ff" xlink:to="loc_us-gaap_ProductMember_eb73821e-0b0f-4f92-9124-88f5ccc39166" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_RoyaltyLicenseAndOtherRevenueMember_84edcf5f-6685-4999-99d5-0d09cfbebdc1" xlink:href="supn-20241231.xsd#supn_RoyaltyLicenseAndOtherRevenueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_537eadbb-8440-4869-9e48-ef327b3bb6ff" xlink:to="loc_supn_RoyaltyLicenseAndOtherRevenueMember_84edcf5f-6685-4999-99d5-0d09cfbebdc1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_eecad4a6-c27c-49ca-a6f6-458a86f739f9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_RevenuesAbstract_eecad4a6-c27c-49ca-a6f6-458a86f739f9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_7b90fa80-e04f-479c-b6ae-f5fe0f4213df" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_eecad4a6-c27c-49ca-a6f6-458a86f739f9" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_7b90fa80-e04f-479c-b6ae-f5fe0f4213df" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_50222120-0f15-4857-bf6d-599a178595f9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_50222120-0f15-4857-bf6d-599a178595f9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_a32f1a23-084c-47c9-afc3-5dd6383d8ef2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_a32f1a23-084c-47c9-afc3-5dd6383d8ef2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_be1e46f9-0cb3-4c91-8397-45c44a062996" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_be1e46f9-0cb3-4c91-8397-45c44a062996" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_24cfa6ed-b5e7-473e-b9cf-2f7a0ae243e6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_24cfa6ed-b5e7-473e-b9cf-2f7a0ae243e6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfIntangibleAssetsExcludingGoodwill_e26009de-e8d4-4e8f-b630-07557f143b88" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ImpairmentOfIntangibleAssetsExcludingGoodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:to="loc_us-gaap_ImpairmentOfIntangibleAssetsExcludingGoodwill_e26009de-e8d4-4e8f-b630-07557f143b88" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_d45723ff-3c26-4e4c-b12c-2e1e22b0c02a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_c8662ced-2fcd-495f-b0f8-aa22a62b5b1b" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_d45723ff-3c26-4e4c-b12c-2e1e22b0c02a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_a5167c03-9002-4bfa-8b25-6ed5cfb2e866" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_CostsAndExpenses_a5167c03-9002-4bfa-8b25-6ed5cfb2e866" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_4c9570f1-e455-48f7-9b46-d5d2b3bbe770" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_OperatingIncomeLoss_4c9570f1-e455-48f7-9b46-d5d2b3bbe770" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_7f4f22e0-2131-445c-9aeb-2cc22211ff75" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNonoperatingIncomeExpenseAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_7f4f22e0-2131-445c-9aeb-2cc22211ff75" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_4e4cb1c2-0035-4df4-ad79-e685d4586061" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_7f4f22e0-2131-445c-9aeb-2cc22211ff75" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_4e4cb1c2-0035-4df4-ad79-e685d4586061" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_d442ed78-0d1a-4800-9ec8-d14248cdff1c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_7f4f22e0-2131-445c-9aeb-2cc22211ff75" xlink:to="loc_us-gaap_InterestExpenseNonoperating_d442ed78-0d1a-4800-9ec8-d14248cdff1c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_99438a15-aad8-43fe-bf14-1742ffd73003" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_7f4f22e0-2131-445c-9aeb-2cc22211ff75" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_99438a15-aad8-43fe-bf14-1742ffd73003" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_3a0c1812-f88b-4129-b4d0-7fc8aa767a70" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_3a0c1812-f88b-4129-b4d0-7fc8aa767a70" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_13973b63-a9a3-4207-9cae-8328f8d954f7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_13973b63-a9a3-4207-9cae-8328f8d954f7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_e569a2c7-7a71-4206-aede-10d0fffd460b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_NetIncomeLoss_e569a2c7-7a71-4206-aede-10d0fffd460b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_EPSBasicAndDilutedAbstract_e83f737a-a099-480d-bed1-303dbabcfef4" xlink:href="supn-20241231.xsd#supn_EPSBasicAndDilutedAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_supn_EPSBasicAndDilutedAbstract_e83f737a-a099-480d-bed1-303dbabcfef4" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_e33904a5-c48e-4b02-a3b4-bc914f5db1c6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_supn_EPSBasicAndDilutedAbstract_e83f737a-a099-480d-bed1-303dbabcfef4" xlink:to="loc_us-gaap_EarningsPerShareBasic_e33904a5-c48e-4b02-a3b4-bc914f5db1c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_0f669e67-3af4-4cea-a5f5-859bdfdaa83e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_supn_EPSBasicAndDilutedAbstract_e83f737a-a099-480d-bed1-303dbabcfef4" xlink:to="loc_us-gaap_EarningsPerShareDiluted_0f669e67-3af4-4cea-a5f5-859bdfdaa83e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_1ccf14ed-222b-4705-8563-b067ebdda03b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ba89d801-7043-431e-86ed-d03eadca3d30" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_1ccf14ed-222b-4705-8563-b067ebdda03b" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_50b44355-d888-4e37-bd20-21581dffb2d9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_1ccf14ed-222b-4705-8563-b067ebdda03b" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_50b44355-d888-4e37-bd20-21581dffb2d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_d38fa7e8-f003-45bd-972e-39a876606c43" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_1ccf14ed-222b-4705-8563-b067ebdda03b" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_d38fa7e8-f003-45bd-972e-39a876606c43" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ConsolidatedStatementsofChangesinStockholdersEquity" xlink:type="simple" xlink:href="supn-20241231.xsd#ConsolidatedStatementsofChangesinStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ConsolidatedStatementsofChangesinStockholdersEquity" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_c2c93500-e648-46f9-846d-252a8500edd6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_8124a9e8-bc3a-4a6f-b587-decb01c0dd02" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_c2c93500-e648-46f9-846d-252a8500edd6" xlink:to="loc_us-gaap_StatementTable_8124a9e8-bc3a-4a6f-b587-decb01c0dd02" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_cafb28d4-eb27-4828-9f4a-f8381fae03bd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_8124a9e8-bc3a-4a6f-b587-decb01c0dd02" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_cafb28d4-eb27-4828-9f4a-f8381fae03bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_cafb28d4-eb27-4828-9f4a-f8381fae03bd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_cafb28d4-eb27-4828-9f4a-f8381fae03bd" xlink:to="loc_us-gaap_EquityComponentDomain_cafb28d4-eb27-4828-9f4a-f8381fae03bd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_5a7d0ed1-f540-4d84-8a97-3a5182c17400" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_cafb28d4-eb27-4828-9f4a-f8381fae03bd" xlink:to="loc_us-gaap_EquityComponentDomain_5a7d0ed1-f540-4d84-8a97-3a5182c17400" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_033bae7e-7abc-450c-9128-3c8c4ea1dcac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5a7d0ed1-f540-4d84-8a97-3a5182c17400" xlink:to="loc_us-gaap_CommonStockMember_033bae7e-7abc-450c-9128-3c8c4ea1dcac" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_e0a16252-9c76-4c31-84b8-82e475148543" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5a7d0ed1-f540-4d84-8a97-3a5182c17400" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_e0a16252-9c76-4c31-84b8-82e475148543" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_8a3bfd68-cb68-49f7-8ba4-23888e53738c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5a7d0ed1-f540-4d84-8a97-3a5182c17400" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_8a3bfd68-cb68-49f7-8ba4-23888e53738c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_580c1824-dd06-4b2c-a3b7-a7f19159115b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5a7d0ed1-f540-4d84-8a97-3a5182c17400" xlink:to="loc_us-gaap_RetainedEarningsMember_580c1824-dd06-4b2c-a3b7-a7f19159115b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_953ab685-a7e4-413c-b4f0-7e5810cb1d8f" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CumulativeEffectPeriodOfAdoptionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_8124a9e8-bc3a-4a6f-b587-decb01c0dd02" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_953ab685-a7e4-413c-b4f0-7e5810cb1d8f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_953ab685-a7e4-413c-b4f0-7e5810cb1d8f_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_953ab685-a7e4-413c-b4f0-7e5810cb1d8f" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_953ab685-a7e4-413c-b4f0-7e5810cb1d8f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_e107bc34-58a7-47bb-bed8-9b9d089e86d2" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_953ab685-a7e4-413c-b4f0-7e5810cb1d8f" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_e107bc34-58a7-47bb-bed8-9b9d089e86d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember_858b6467-7ef1-4219-940d-381cd074aa94" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_e107bc34-58a7-47bb-bed8-9b9d089e86d2" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember_858b6467-7ef1-4219-940d-381cd074aa94" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustedBalanceMember_2d209e01-3a7c-476b-a15c-f3980381a16b" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CumulativeEffectPeriodOfAdoptionAdjustedBalanceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_e107bc34-58a7-47bb-bed8-9b9d089e86d2" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustedBalanceMember_2d209e01-3a7c-476b-a15c-f3980381a16b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c2c93500-e648-46f9-846d-252a8500edd6" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_d27943e0-cc8d-4375-a17d-562732746da1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_d27943e0-cc8d-4375-a17d-562732746da1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_73560348-3a3a-4f8d-ace9-fb5d28ca6c3f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:to="loc_us-gaap_StockholdersEquity_73560348-3a3a-4f8d-ace9-fb5d28ca6c3f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_a81afe77-64a4-4d1e-ad12-f2fcc725547a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_a81afe77-64a4-4d1e-ad12-f2fcc725547a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_a03e1fbe-6c61-4391-b571-c49f77db8326" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_a03e1fbe-6c61-4391-b571-c49f77db8326" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_01a59d41-0ab0-4615-87e3-be344777c713" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_01a59d41-0ab0-4615-87e3-be344777c713" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_bda42553-f076-4257-848d-6d693a961b6a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:to="loc_us-gaap_NetIncomeLoss_bda42553-f076-4257-848d-6d693a961b6a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_f58ee5e7-a7c9-4a8c-bedd-8adf1ac2840c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_88d0802c-858a-4881-9410-2c1472e0c8bf" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_f58ee5e7-a7c9-4a8c-bedd-8adf1ac2840c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_424605a9-d173-45a5-bf36-a2e308917a39" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_7022088c-9498-4042-ba24-5e2cdba7bf2f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesAccountsReceivableNetandConcentrationofCreditRiskDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#SummaryofSignificantAccountingPoliciesAccountsReceivableNetandConcentrationofCreditRiskDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesAccountsReceivableNetandConcentrationofCreditRiskDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskLineItems_afb491cd-84b2-413f-aa98-51f9a4fa7612" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTable_b08baf09-971f-4f6c-bd04-4410f7d7db9e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ConcentrationRiskLineItems_afb491cd-84b2-413f-aa98-51f9a4fa7612" xlink:to="loc_us-gaap_ConcentrationRiskTable_b08baf09-971f-4f6c-bd04-4410f7d7db9e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_ba777536-19c2-4922-9dc4-5dbfcddbdafa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ConcentrationRiskTable_b08baf09-971f-4f6c-bd04-4410f7d7db9e" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_ba777536-19c2-4922-9dc4-5dbfcddbdafa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_ba777536-19c2-4922-9dc4-5dbfcddbdafa_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_ba777536-19c2-4922-9dc4-5dbfcddbdafa" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_ba777536-19c2-4922-9dc4-5dbfcddbdafa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_98159cae-9732-43b7-9c03-a1907213627f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_ba777536-19c2-4922-9dc4-5dbfcddbdafa" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_98159cae-9732-43b7-9c03-a1907213627f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_3590d9b0-27fc-4fb8-9668-c87947624f59" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_98159cae-9732-43b7-9c03-a1907213627f" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_3590d9b0-27fc-4fb8-9668-c87947624f59" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_d8353a46-9be8-4872-b11f-ebbfc850f13e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ConcentrationRiskTable_b08baf09-971f-4f6c-bd04-4410f7d7db9e" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_d8353a46-9be8-4872-b11f-ebbfc850f13e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_d8353a46-9be8-4872-b11f-ebbfc850f13e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_d8353a46-9be8-4872-b11f-ebbfc850f13e" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_d8353a46-9be8-4872-b11f-ebbfc850f13e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_6faa2a12-389d-4863-81f0-ef34d6c1ceaa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_d8353a46-9be8-4872-b11f-ebbfc850f13e" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_6faa2a12-389d-4863-81f0-ef34d6c1ceaa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerMember_96be7574-ad5d-45b7-9766-4c6ed0deaa25" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_6faa2a12-389d-4863-81f0-ef34d6c1ceaa" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerMember_96be7574-ad5d-45b7-9766-4c6ed0deaa25" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_51dee945-18e4-4471-bd7b-917fc15ac4f9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_6faa2a12-389d-4863-81f0-ef34d6c1ceaa" xlink:to="loc_us-gaap_AccountsReceivableMember_51dee945-18e4-4471-bd7b-917fc15ac4f9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_0b467c0a-3a0b-4e89-91b4-873c134e1390" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ConcentrationRiskTable_b08baf09-971f-4f6c-bd04-4410f7d7db9e" xlink:to="loc_srt_MajorCustomersAxis_0b467c0a-3a0b-4e89-91b4-873c134e1390" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_0b467c0a-3a0b-4e89-91b4-873c134e1390_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_0b467c0a-3a0b-4e89-91b4-873c134e1390" xlink:to="loc_srt_NameOfMajorCustomerDomain_0b467c0a-3a0b-4e89-91b4-873c134e1390_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_6b400b95-ebaa-49c9-a7c3-82438d6cf2c4" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_0b467c0a-3a0b-4e89-91b4-873c134e1390" xlink:to="loc_srt_NameOfMajorCustomerDomain_6b400b95-ebaa-49c9-a7c3-82438d6cf2c4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_AllMajorCustomersMember_2e98499d-f0e5-49e7-a50f-3b3f95df6521" xlink:href="supn-20241231.xsd#supn_AllMajorCustomersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_6b400b95-ebaa-49c9-a7c3-82438d6cf2c4" xlink:to="loc_supn_AllMajorCustomersMember_2e98499d-f0e5-49e7-a50f-3b3f95df6521" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CustomerAMember_e0cf563b-5a6a-49a1-9b15-059d9380946e" xlink:href="supn-20241231.xsd#supn_CustomerAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_supn_AllMajorCustomersMember_2e98499d-f0e5-49e7-a50f-3b3f95df6521" xlink:to="loc_supn_CustomerAMember_e0cf563b-5a6a-49a1-9b15-059d9380946e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CustomerBMember_09168c6e-071b-4508-bd83-5ef36b7dc492" xlink:href="supn-20241231.xsd#supn_CustomerBMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_supn_AllMajorCustomersMember_2e98499d-f0e5-49e7-a50f-3b3f95df6521" xlink:to="loc_supn_CustomerBMember_09168c6e-071b-4508-bd83-5ef36b7dc492" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CustomerCMember_a7bb8d3b-d138-48e4-ab9e-c2960dc3abe1" xlink:href="supn-20241231.xsd#supn_CustomerCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_supn_AllMajorCustomersMember_2e98499d-f0e5-49e7-a50f-3b3f95df6521" xlink:to="loc_supn_CustomerCMember_a7bb8d3b-d138-48e4-ab9e-c2960dc3abe1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CustomerDMember_5955a5b8-4d5a-4d1c-a692-97d59800fe4b" xlink:href="supn-20241231.xsd#supn_CustomerDMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_supn_AllMajorCustomersMember_2e98499d-f0e5-49e7-a50f-3b3f95df6521" xlink:to="loc_supn_CustomerDMember_5955a5b8-4d5a-4d1c-a692-97d59800fe4b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetAbstract_22821867-187c-4848-9aa0-1a1c77a7598e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsReceivableNetAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskLineItems_afb491cd-84b2-413f-aa98-51f9a4fa7612" xlink:to="loc_us-gaap_AccountsReceivableNetAbstract_22821867-187c-4848-9aa0-1a1c77a7598e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_6ff7a8a5-6e83-4d5f-adbe-922299681ade" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccountsReceivableNetAbstract_22821867-187c-4848-9aa0-1a1c77a7598e" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_6ff7a8a5-6e83-4d5f-adbe-922299681ade" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesPropertyandEquipmentUsefulLifeDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#SummaryofSignificantAccountingPoliciesPropertyandEquipmentUsefulLifeDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesPropertyandEquipmentUsefulLifeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_c386b63d-4396-4c94-b76c-6cb4fb51a9ab" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_ef7e469c-d099-47a8-b892-426dbac77d49" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_c386b63d-4396-4c94-b76c-6cb4fb51a9ab" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_ef7e469c-d099-47a8-b892-426dbac77d49" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_a224360f-442c-467c-967f-c6d4fdbe132d" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_ef7e469c-d099-47a8-b892-426dbac77d49" xlink:to="loc_srt_RangeAxis_a224360f-442c-467c-967f-c6d4fdbe132d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_a224360f-442c-467c-967f-c6d4fdbe132d_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_a224360f-442c-467c-967f-c6d4fdbe132d" xlink:to="loc_srt_RangeMember_a224360f-442c-467c-967f-c6d4fdbe132d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_7c4881ff-f857-4538-be6c-71bf7d28d34b" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_a224360f-442c-467c-967f-c6d4fdbe132d" xlink:to="loc_srt_RangeMember_7c4881ff-f857-4538-be6c-71bf7d28d34b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_a238b27a-583c-4a75-81a9-8ec2cfe53937" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_7c4881ff-f857-4538-be6c-71bf7d28d34b" xlink:to="loc_srt_MinimumMember_a238b27a-583c-4a75-81a9-8ec2cfe53937" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_45d422cb-28a7-4a75-9235-9ac12d3011da" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_7c4881ff-f857-4538-be6c-71bf7d28d34b" xlink:to="loc_srt_MaximumMember_45d422cb-28a7-4a75-9235-9ac12d3011da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_aeeecb22-1e1c-4394-a410-43a11e1f451b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_ef7e469c-d099-47a8-b892-426dbac77d49" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_aeeecb22-1e1c-4394-a410-43a11e1f451b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_aeeecb22-1e1c-4394-a410-43a11e1f451b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_aeeecb22-1e1c-4394-a410-43a11e1f451b" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_aeeecb22-1e1c-4394-a410-43a11e1f451b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_cbb568f8-57bf-483a-a17b-52eee994ea70" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_aeeecb22-1e1c-4394-a410-43a11e1f451b" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_cbb568f8-57bf-483a-a17b-52eee994ea70" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_014b2190-5155-4dd9-8e98-53676f4d0094" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_cbb568f8-57bf-483a-a17b-52eee994ea70" xlink:to="loc_us-gaap_ComputerEquipmentMember_014b2190-5155-4dd9-8e98-53676f4d0094" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_b1c35aaf-13e5-4d4f-ac96-aeae1c333ea7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SoftwareAndSoftwareDevelopmentCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_cbb568f8-57bf-483a-a17b-52eee994ea70" xlink:to="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_b1c35aaf-13e5-4d4f-ac96-aeae1c333ea7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_a56db661-7601-4341-b2ed-7a881818eae0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_cbb568f8-57bf-483a-a17b-52eee994ea70" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_a56db661-7601-4341-b2ed-7a881818eae0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_17fe9859-a1a1-4839-9f73-9c18e291e0eb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_c386b63d-4396-4c94-b76c-6cb4fb51a9ab" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_17fe9859-a1a1-4839-9f73-9c18e291e0eb" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesRevenueRecognitionDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#SummaryofSignificantAccountingPoliciesRevenueRecognitionDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesRevenueRecognitionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_cb9adb64-9d90-4a96-9c28-d7b203ac24c7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_cb9adb64-9d90-4a96-9c28-d7b203ac24c7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_53b1a430-1b15-4e0d-9417-a842d0c54747" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_cb9adb64-9d90-4a96-9c28-d7b203ac24c7" xlink:to="loc_srt_RangeAxis_53b1a430-1b15-4e0d-9417-a842d0c54747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_53b1a430-1b15-4e0d-9417-a842d0c54747_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_53b1a430-1b15-4e0d-9417-a842d0c54747" xlink:to="loc_srt_RangeMember_53b1a430-1b15-4e0d-9417-a842d0c54747_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_17f3f42d-e874-4ecd-bb3a-52ed5e23e357" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_53b1a430-1b15-4e0d-9417-a842d0c54747" xlink:to="loc_srt_RangeMember_17f3f42d-e874-4ecd-bb3a-52ed5e23e357" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_b383b3a5-659b-48fe-8216-c816936273fe" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_17f3f42d-e874-4ecd-bb3a-52ed5e23e357" xlink:to="loc_srt_MaximumMember_b383b3a5-659b-48fe-8216-c816936273fe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_3223a3ce-32f0-4908-a2dd-517c82314efa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_cb9adb64-9d90-4a96-9c28-d7b203ac24c7" xlink:to="loc_us-gaap_TypeOfArrangementAxis_3223a3ce-32f0-4908-a2dd-517c82314efa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_3223a3ce-32f0-4908-a2dd-517c82314efa_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_3223a3ce-32f0-4908-a2dd-517c82314efa" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_3223a3ce-32f0-4908-a2dd-517c82314efa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ebe54b73-c0cc-4367-b855-83a8da1e2757" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_3223a3ce-32f0-4908-a2dd-517c82314efa" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ebe54b73-c0cc-4367-b855-83a8da1e2757" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RoyaltyAgreementsMember_26f3a1c4-6bec-44ce-9965-d42c2a950d8b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RoyaltyAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ebe54b73-c0cc-4367-b855-83a8da1e2757" xlink:to="loc_us-gaap_RoyaltyAgreementsMember_26f3a1c4-6bec-44ce-9965-d42c2a950d8b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerAssetNet_4a00d62b-ff68-4dad-bf58-988c88fc0893" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerAssetNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:to="loc_us-gaap_ContractWithCustomerAssetNet_4a00d62b-ff68-4dad-bf58-988c88fc0893" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_4a6433a8-b266-456f-a091-ef8487245255" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:to="loc_us-gaap_ContractWithCustomerLiability_4a6433a8-b266-456f-a091-ef8487245255" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_SalesReturnPeriodPriorToExpiration_597df31e-1cbb-4e1b-8661-f41f05e470b9" xlink:href="supn-20241231.xsd#supn_SalesReturnPeriodPriorToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:to="loc_supn_SalesReturnPeriodPriorToExpiration_597df31e-1cbb-4e1b-8661-f41f05e470b9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_SalesReturnPeriod_9f1e74a5-4ff9-4555-aaca-84705c80c642" xlink:href="supn-20241231.xsd#supn_SalesReturnPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:to="loc_supn_SalesReturnPeriod_9f1e74a5-4ff9-4555-aaca-84705c80c642" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_ProductsShelfLife_7ffab752-684e-48a3-9653-1665f417eb1f" xlink:href="supn-20241231.xsd#supn_ProductsShelfLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:to="loc_supn_ProductsShelfLife_7ffab752-684e-48a3-9653-1665f417eb1f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MinimumGuaranteedAmountsOwedToCompany_4c5b7429-1114-49ff-a986-6afe5f544d98" xlink:href="supn-20241231.xsd#supn_MinimumGuaranteedAmountsOwedToCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_a0d18640-fac6-4519-8d3a-1c1c8908fa39" xlink:to="loc_supn_MinimumGuaranteedAmountsOwedToCompany_4c5b7429-1114-49ff-a986-6afe5f544d98" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesSharebasedCompensationDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#SummaryofSignificantAccountingPoliciesSharebasedCompensationDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesSharebasedCompensationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3f11c84c-d966-4977-b8c2-518860e7f1f6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_06eae8b5-83ba-4cdd-b2c6-c03c7e1970a4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3f11c84c-d966-4977-b8c2-518860e7f1f6" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_06eae8b5-83ba-4cdd-b2c6-c03c7e1970a4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_3c3015d2-782e-4085-b2d2-b1764d279ab1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_06eae8b5-83ba-4cdd-b2c6-c03c7e1970a4" xlink:to="loc_us-gaap_AwardTypeAxis_3c3015d2-782e-4085-b2d2-b1764d279ab1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_3c3015d2-782e-4085-b2d2-b1764d279ab1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_3c3015d2-782e-4085-b2d2-b1764d279ab1" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_3c3015d2-782e-4085-b2d2-b1764d279ab1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_67a6c019-aa09-4c83-a707-1894141b866a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_3c3015d2-782e-4085-b2d2-b1764d279ab1" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_67a6c019-aa09-4c83-a707-1894141b866a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_6a442d52-3c57-4c32-be83-bd12370767e0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_67a6c019-aa09-4c83-a707-1894141b866a" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_6a442d52-3c57-4c32-be83-bd12370767e0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualAxis_c21ec9bd-59d5-487c-b74e-d70b0ec54c8d" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_TitleOfIndividualAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_06eae8b5-83ba-4cdd-b2c6-c03c7e1970a4" xlink:to="loc_srt_TitleOfIndividualAxis_c21ec9bd-59d5-487c-b74e-d70b0ec54c8d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_c21ec9bd-59d5-487c-b74e-d70b0ec54c8d_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_TitleOfIndividualAxis_c21ec9bd-59d5-487c-b74e-d70b0ec54c8d" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_c21ec9bd-59d5-487c-b74e-d70b0ec54c8d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_2364d9c2-9ef4-40ac-a699-d12e71386f47" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_TitleOfIndividualAxis_c21ec9bd-59d5-487c-b74e-d70b0ec54c8d" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_2364d9c2-9ef4-40ac-a699-d12e71386f47" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_DirectorMember_68da619b-568e-450d-b1b5-99e1e81a2389" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_DirectorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_2364d9c2-9ef4-40ac-a699-d12e71386f47" xlink:to="loc_srt_DirectorMember_68da619b-568e-450d-b1b5-99e1e81a2389" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_0fb7ab9d-58d9-451b-9608-eeb88cdefb4d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3f11c84c-d966-4977-b8c2-518860e7f1f6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_0fb7ab9d-58d9-451b-9608-eeb88cdefb4d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_8e37b8ee-69af-4396-b641-7b136315f6a2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3f11c84c-d966-4977-b8c2-518860e7f1f6" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_8e37b8ee-69af-4396-b641-7b136315f6a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_0aa94553-a5d5-4817-82a1-070f35687993" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_3f11c84c-d966-4977-b8c2-518860e7f1f6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_0aa94553-a5d5-4817-82a1-070f35687993" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesInterestExpenseDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#SummaryofSignificantAccountingPoliciesInterestExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/SummaryofSignificantAccountingPoliciesInterestExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_b11cc328-4f49-412a-a8a9-a0bbecd58e69" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_1f8fc37a-f6dc-41dd-81c5-a5c671e22f33" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_b11cc328-4f49-412a-a8a9-a0bbecd58e69" xlink:to="loc_us-gaap_DebtInstrumentTable_1f8fc37a-f6dc-41dd-81c5-a5c671e22f33" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_eaed4c5d-aed7-46ea-9220-1c695668b3a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_1f8fc37a-f6dc-41dd-81c5-a5c671e22f33" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_eaed4c5d-aed7-46ea-9220-1c695668b3a8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_eaed4c5d-aed7-46ea-9220-1c695668b3a8_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_eaed4c5d-aed7-46ea-9220-1c695668b3a8" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_eaed4c5d-aed7-46ea-9220-1c695668b3a8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_02844a87-c1ea-4e08-a524-d7f45197b183" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_eaed4c5d-aed7-46ea-9220-1c695668b3a8" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_02844a87-c1ea-4e08-a524-d7f45197b183" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayableMember_ed0928de-1203-432a-84d3-21a43bd18f34" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleNotesPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_02844a87-c1ea-4e08-a524-d7f45197b183" xlink:to="loc_us-gaap_ConvertibleNotesPayableMember_ed0928de-1203-432a-84d3-21a43bd18f34" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentageAbstract_520c3d9d-9e58-4526-94a0-58080c09f12a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentageAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_b11cc328-4f49-412a-a8a9-a0bbecd58e69" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentageAbstract_520c3d9d-9e58-4526-94a0-58080c09f12a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_5298a06d-7a8f-4fe5-9af7-a7680bd68ac1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentInterestRateStatedPercentageAbstract_520c3d9d-9e58-4526-94a0-58080c09f12a" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_5298a06d-7a8f-4fe5-9af7-a7680bd68ac1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_7a93f715-f194-4348-992f-4cd37d4de468" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentInterestRateStatedPercentageAbstract_520c3d9d-9e58-4526-94a0-58080c09f12a" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_7a93f715-f194-4348-992f-4cd37d4de468" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/DisaggregatedRevenuesScheduleofRevenuesDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#DisaggregatedRevenuesScheduleofRevenuesDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/DisaggregatedRevenuesScheduleofRevenuesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_2f456a4a-8839-4f29-97b5-afb6908dd052" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_f14fc4c5-a79b-49c9-9061-2ec2c2452edc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_2f456a4a-8839-4f29-97b5-afb6908dd052" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_f14fc4c5-a79b-49c9-9061-2ec2c2452edc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_991430de-3bee-4caa-b423-a93cf5bd5f51" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_f14fc4c5-a79b-49c9-9061-2ec2c2452edc" xlink:to="loc_srt_ProductOrServiceAxis_991430de-3bee-4caa-b423-a93cf5bd5f51" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_991430de-3bee-4caa-b423-a93cf5bd5f51_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_991430de-3bee-4caa-b423-a93cf5bd5f51" xlink:to="loc_srt_ProductsAndServicesDomain_991430de-3bee-4caa-b423-a93cf5bd5f51_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_a1dc75f7-fa78-406c-9f85-2d7b6fd6dc63" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_991430de-3bee-4caa-b423-a93cf5bd5f51" xlink:to="loc_srt_ProductsAndServicesDomain_a1dc75f7-fa78-406c-9f85-2d7b6fd6dc63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_a1dc75f7-fa78-406c-9f85-2d7b6fd6dc63" xlink:to="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_QelbreeMember_8d0f68d1-0319-4697-80b2-47586804e1ad" xlink:href="supn-20241231.xsd#supn_QelbreeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:to="loc_supn_QelbreeMember_8d0f68d1-0319-4697-80b2-47586804e1ad" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_GOCOVRIMember_881925fa-e9dd-41ca-a23f-fe9f62b1ca73" xlink:href="supn-20241231.xsd#supn_GOCOVRIMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:to="loc_supn_GOCOVRIMember_881925fa-e9dd-41ca-a23f-fe9f62b1ca73" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_OxtellarXRMember_3ff6f767-95b8-4ce6-a310-c8a9d7b09407" xlink:href="supn-20241231.xsd#supn_OxtellarXRMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:to="loc_supn_OxtellarXRMember_3ff6f767-95b8-4ce6-a310-c8a9d7b09407" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_APOKYNMember_e64a866d-0698-45ea-98ed-e06addbef17d" xlink:href="supn-20241231.xsd#supn_APOKYNMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:to="loc_supn_APOKYNMember_e64a866d-0698-45ea-98ed-e06addbef17d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_TrokendiXrMember_0d733ed7-fcd5-459c-816d-eede11fdf9bd" xlink:href="supn-20241231.xsd#supn_TrokendiXrMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:to="loc_supn_TrokendiXrMember_0d733ed7-fcd5-459c-816d-eede11fdf9bd" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ManufacturedProductOtherMember_29beccbf-f191-4794-a38f-d59fef094b26" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ManufacturedProductOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_b16bf72e-d42a-4cf1-a781-a10027297ca0" xlink:to="loc_us-gaap_ManufacturedProductOtherMember_29beccbf-f191-4794-a38f-d59fef094b26" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_RoyaltyLicenseAndOtherRevenueMember_2676ba48-7e2f-4f35-b597-0f40aa45fd92" xlink:href="supn-20241231.xsd#supn_RoyaltyLicenseAndOtherRevenueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_a1dc75f7-fa78-406c-9f85-2d7b6fd6dc63" xlink:to="loc_supn_RoyaltyLicenseAndOtherRevenueMember_2676ba48-7e2f-4f35-b597-0f40aa45fd92" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_cbd1949f-c169-4b66-b47c-23459f55699c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_2f456a4a-8839-4f29-97b5-afb6908dd052" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_cbd1949f-c169-4b66-b47c-23459f55699c" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/DisaggregatedRevenuesScheduleofPercentageofNetProductSalestoTotalNetProductSalesDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#DisaggregatedRevenuesScheduleofPercentageofNetProductSalestoTotalNetProductSalesDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/DisaggregatedRevenuesScheduleofPercentageofNetProductSalestoTotalNetProductSalesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_12d1a5b0-d75d-4ec5-bacd-1ce96379d9f6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_3c5bdcae-ef69-4c30-8a73-ee8844adeb83" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_12d1a5b0-d75d-4ec5-bacd-1ce96379d9f6" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_3c5bdcae-ef69-4c30-8a73-ee8844adeb83" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_42b4f002-0212-40ea-b325-7118d493804c" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_3c5bdcae-ef69-4c30-8a73-ee8844adeb83" xlink:to="loc_srt_ProductOrServiceAxis_42b4f002-0212-40ea-b325-7118d493804c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_42b4f002-0212-40ea-b325-7118d493804c_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_42b4f002-0212-40ea-b325-7118d493804c" xlink:to="loc_srt_ProductsAndServicesDomain_42b4f002-0212-40ea-b325-7118d493804c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_09ce994f-ffd4-4800-9b62-75ade3f2bf84" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_42b4f002-0212-40ea-b325-7118d493804c" xlink:to="loc_srt_ProductsAndServicesDomain_09ce994f-ffd4-4800-9b62-75ade3f2bf84" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_09ce994f-ffd4-4800-9b62-75ade3f2bf84" xlink:to="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_QelbreeMember_f6131b1d-783d-4ed8-9378-3ec9e65590de" xlink:href="supn-20241231.xsd#supn_QelbreeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:to="loc_supn_QelbreeMember_f6131b1d-783d-4ed8-9378-3ec9e65590de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_GOCOVRIMember_a3bee453-56f1-498f-9f72-5461f2e48cdc" xlink:href="supn-20241231.xsd#supn_GOCOVRIMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:to="loc_supn_GOCOVRIMember_a3bee453-56f1-498f-9f72-5461f2e48cdc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_OxtellarXRMember_83b9b3ad-2d6d-4d1a-8e47-e3506b043c90" xlink:href="supn-20241231.xsd#supn_OxtellarXRMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:to="loc_supn_OxtellarXRMember_83b9b3ad-2d6d-4d1a-8e47-e3506b043c90" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_APOKYNMember_9b7b4223-af56-4537-a687-b2c264d1d697" xlink:href="supn-20241231.xsd#supn_APOKYNMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:to="loc_supn_APOKYNMember_9b7b4223-af56-4537-a687-b2c264d1d697" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_TrokendiXrMember_7fc6325e-22d8-4a5d-ab37-d35b25881685" xlink:href="supn-20241231.xsd#supn_TrokendiXrMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:to="loc_supn_TrokendiXrMember_7fc6325e-22d8-4a5d-ab37-d35b25881685" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ManufacturedProductOtherMember_15af1105-31be-4d97-acd3-8437d260cec1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ManufacturedProductOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_557d8ea8-10e2-42a8-949d-44399aceb035" xlink:to="loc_us-gaap_ManufacturedProductOtherMember_15af1105-31be-4d97-acd3-8437d260cec1" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_30effc59-d9c9-4678-bae9-dd4cde40503c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_3c5bdcae-ef69-4c30-8a73-ee8844adeb83" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_30effc59-d9c9-4678-bae9-dd4cde40503c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_30effc59-d9c9-4678-bae9-dd4cde40503c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_30effc59-d9c9-4678-bae9-dd4cde40503c" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_30effc59-d9c9-4678-bae9-dd4cde40503c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_27c12766-c2b8-415d-8798-70c5991cbf98" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_30effc59-d9c9-4678-bae9-dd4cde40503c" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_27c12766-c2b8-415d-8798-70c5991cbf98" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerMember_7f3a13c4-2d5a-45fc-8a89-b5bce1657933" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_27c12766-c2b8-415d-8798-70c5991cbf98" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerMember_7f3a13c4-2d5a-45fc-8a89-b5bce1657933" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_347f313e-78a8-4c0e-8b0b-2591fe3536ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_3c5bdcae-ef69-4c30-8a73-ee8844adeb83" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_347f313e-78a8-4c0e-8b0b-2591fe3536ba" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_347f313e-78a8-4c0e-8b0b-2591fe3536ba_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_347f313e-78a8-4c0e-8b0b-2591fe3536ba" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_347f313e-78a8-4c0e-8b0b-2591fe3536ba_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_e5be7001-b0d1-4444-a405-52f52ca33e02" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_347f313e-78a8-4c0e-8b0b-2591fe3536ba" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_e5be7001-b0d1-4444-a405-52f52ca33e02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductConcentrationRiskMember_720ef697-cf5a-481c-8a59-3adbc1becb41" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProductConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_e5be7001-b0d1-4444-a405-52f52ca33e02" xlink:to="loc_us-gaap_ProductConcentrationRiskMember_720ef697-cf5a-481c-8a59-3adbc1becb41" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_6ca6f07b-ca30-4662-b07d-715e7c14a18b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_12d1a5b0-d75d-4ec5-bacd-1ce96379d9f6" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_6ca6f07b-ca30-4662-b07d-715e7c14a18b" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/InvestmentsNarrativeDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#InvestmentsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/InvestmentsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableInterestEntityLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_248fed44-18c3-4020-9710-f8bb243f6f19" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfVariableInterestEntitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_248fed44-18c3-4020-9710-f8bb243f6f19" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_4651c644-dbfe-497f-b6ca-cf864df938f3" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_248fed44-18c3-4020-9710-f8bb243f6f19" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_4651c644-dbfe-497f-b6ca-cf864df938f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_4651c644-dbfe-497f-b6ca-cf864df938f3_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_4651c644-dbfe-497f-b6ca-cf864df938f3" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_4651c644-dbfe-497f-b6ca-cf864df938f3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_d1f4df4e-a528-4c61-bdaa-3e34407f7562" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_4651c644-dbfe-497f-b6ca-cf864df938f3" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_d1f4df4e-a528-4c61-bdaa-3e34407f7562" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_NavitorPharmaceuticalsIncMember_eafea177-43c7-4d05-adeb-759e6a9bf187" xlink:href="supn-20241231.xsd#supn_NavitorPharmaceuticalsIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_d1f4df4e-a528-4c61-bdaa-3e34407f7562" xlink:to="loc_supn_NavitorPharmaceuticalsIncMember_eafea177-43c7-4d05-adeb-759e6a9bf187" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesAxis_35fca0f6-87ff-4325-98dc-4f2d55762be4" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ConsolidatedEntitiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_248fed44-18c3-4020-9710-f8bb243f6f19" xlink:to="loc_srt_ConsolidatedEntitiesAxis_35fca0f6-87ff-4325-98dc-4f2d55762be4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_35fca0f6-87ff-4325-98dc-4f2d55762be4_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ConsolidatedEntitiesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ConsolidatedEntitiesAxis_35fca0f6-87ff-4325-98dc-4f2d55762be4" xlink:to="loc_srt_ConsolidatedEntitiesDomain_35fca0f6-87ff-4325-98dc-4f2d55762be4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_df4512fe-54f6-4733-95fd-7bba22ba08a9" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ConsolidatedEntitiesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ConsolidatedEntitiesAxis_35fca0f6-87ff-4325-98dc-4f2d55762be4" xlink:to="loc_srt_ConsolidatedEntitiesDomain_df4512fe-54f6-4733-95fd-7bba22ba08a9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_2fc0027c-455e-4f74-9f36-6c0ff30dc19c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ConsolidatedEntitiesDomain_df4512fe-54f6-4733-95fd-7bba22ba08a9" xlink:to="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_2fc0027c-455e-4f74-9f36-6c0ff30dc19c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_daa1f754-0220-4587-a92e-7e07bd75d236" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_248fed44-18c3-4020-9710-f8bb243f6f19" xlink:to="loc_srt_RangeAxis_daa1f754-0220-4587-a92e-7e07bd75d236" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_daa1f754-0220-4587-a92e-7e07bd75d236_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_daa1f754-0220-4587-a92e-7e07bd75d236" xlink:to="loc_srt_RangeMember_daa1f754-0220-4587-a92e-7e07bd75d236_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_8bbca4e5-d380-4356-a34c-8e0c327f4b43" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_daa1f754-0220-4587-a92e-7e07bd75d236" xlink:to="loc_srt_RangeMember_8bbca4e5-d380-4356-a34c-8e0c327f4b43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_37592820-9740-41ac-bfbe-6bd6730e7d3d" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_8bbca4e5-d380-4356-a34c-8e0c327f4b43" xlink:to="loc_srt_MinimumMember_37592820-9740-41ac-bfbe-6bd6730e7d3d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_f6dcab23-0e9a-488b-a24e-c3d735d2c8aa" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_8bbca4e5-d380-4356-a34c-8e0c327f4b43" xlink:to="loc_srt_MaximumMember_f6dcab23-0e9a-488b-a24e-c3d735d2c8aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestAllowanceForCreditLossNotPreviouslyRecorded_e3234125-4386-4a79-b85f-077b1725aab9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestAllowanceForCreditLossNotPreviouslyRecorded"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestAllowanceForCreditLossNotPreviouslyRecorded_e3234125-4386-4a79-b85f-077b1725aab9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CollaborativeArrangementThresholdForDevelopmentCostsPayments_2eb13988-13c7-4dd0-977a-aa1febae42fd" xlink:href="supn-20241231.xsd#supn_CollaborativeArrangementThresholdForDevelopmentCostsPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_supn_CollaborativeArrangementThresholdForDevelopmentCostsPayments_2eb13988-13c7-4dd0-977a-aa1febae42fd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CollaborativeArrangementPaymentForOneTimeFee_27983431-8b83-4f54-98da-7f3a4a3f3b3d" xlink:href="supn-20241231.xsd#supn_CollaborativeArrangementPaymentForOneTimeFee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_supn_CollaborativeArrangementPaymentForOneTimeFee_27983431-8b83-4f54-98da-7f3a4a3f3b3d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiCost_d207c81d-96eb-41d3-858b-9a1fb828700c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquitySecuritiesFvNiCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_us-gaap_EquitySecuritiesFvNiCost_d207c81d-96eb-41d3-858b-9a1fb828700c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityOwnershipPercentage_0e408cd0-9d33-4ef8-bc16-1b193194f45b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableInterestEntityOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_us-gaap_VariableInterestEntityOwnershipPercentage_0e408cd0-9d33-4ef8-bc16-1b193194f45b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CollaborativeArrangementExpectedDevelopmentCosts_0a735576-6301-45f5-a5cb-0a5e5315e866" xlink:href="supn-20241231.xsd#supn_CollaborativeArrangementExpectedDevelopmentCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_supn_CollaborativeArrangementExpectedDevelopmentCosts_0a735576-6301-45f5-a5cb-0a5e5315e866" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_CollaborativeArrangementUpfrontDevelopmentCosts_19542a61-85da-4164-a997-97917570a230" xlink:href="supn-20241231.xsd#supn_CollaborativeArrangementUpfrontDevelopmentCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_supn_CollaborativeArrangementUpfrontDevelopmentCosts_19542a61-85da-4164-a997-97917570a230" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDivestitureOfBusinessesAndInterestsInAffiliates_1c4802a0-2c55-4c10-b3c6-fdd3a58ee614" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromDivestitureOfBusinessesAndInterestsInAffiliates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_us-gaap_ProceedsFromDivestitureOfBusinessesAndInterestsInAffiliates_1c4802a0-2c55-4c10-b3c6-fdd3a58ee614" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentRealizedGainLossOnDisposal_80a28278-8dcc-4ee5-b35f-43edf4a588bb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityMethodInvestmentRealizedGainLossOnDisposal"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_5b21bc99-55c9-4421-a7af-c8c4f6196ae7" xlink:to="loc_us-gaap_EquityMethodInvestmentRealizedGainLossOnDisposal_80a28278-8dcc-4ee5-b35f-43edf4a588bb" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/FairValueofFinancialInstrumentsDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#FairValueofFinancialInstrumentsDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/FairValueofFinancialInstrumentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2b847ef5-3275-4526-a936-f068b85708c1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4e4e2e10-5e25-4643-89c3-022b6041ffb9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2b847ef5-3275-4526-a936-f068b85708c1" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4e4e2e10-5e25-4643-89c3-022b6041ffb9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_62a23e53-03f5-46a1-97e5-5f4a620c7cee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4e4e2e10-5e25-4643-89c3-022b6041ffb9" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_62a23e53-03f5-46a1-97e5-5f4a620c7cee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_62a23e53-03f5-46a1-97e5-5f4a620c7cee_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_62a23e53-03f5-46a1-97e5-5f4a620c7cee" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_62a23e53-03f5-46a1-97e5-5f4a620c7cee_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_b1a9386d-fdbd-493a-b2c5-73de94591348" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_62a23e53-03f5-46a1-97e5-5f4a620c7cee" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_b1a9386d-fdbd-493a-b2c5-73de94591348" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_7d6c9f4f-8856-44d3-b15d-e45a641fd4b9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_b1a9386d-fdbd-493a-b2c5-73de94591348" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_7d6c9f4f-8856-44d3-b15d-e45a641fd4b9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_14566389-31c3-446c-a8ee-253896c6c58e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4e4e2e10-5e25-4643-89c3-022b6041ffb9" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_14566389-31c3-446c-a8ee-253896c6c58e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_14566389-31c3-446c-a8ee-253896c6c58e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_14566389-31c3-446c-a8ee-253896c6c58e" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_14566389-31c3-446c-a8ee-253896c6c58e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb30888b-64e5-4810-9fd3-d6a907b810f5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_14566389-31c3-446c-a8ee-253896c6c58e" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb30888b-64e5-4810-9fd3-d6a907b810f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_e722eae7-7808-4072-b55b-aff18ecfb8cb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb30888b-64e5-4810-9fd3-d6a907b810f5" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_e722eae7-7808-4072-b55b-aff18ecfb8cb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_b4e0197f-3ff3-49f9-ba35-d6c4ead7a17d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb30888b-64e5-4810-9fd3-d6a907b810f5" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_b4e0197f-3ff3-49f9-ba35-d6c4ead7a17d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_4d034ded-aa48-497a-af98-13918e5f4d03" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb30888b-64e5-4810-9fd3-d6a907b810f5" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_4d034ded-aa48-497a-af98-13918e5f4d03" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAxis_aa80d968-4f91-4f00-b5a1-a421174f5a60" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4e4e2e10-5e25-4643-89c3-022b6041ffb9" xlink:to="loc_us-gaap_CashAndCashEquivalentsAxis_aa80d968-4f91-4f00-b5a1-a421174f5a60" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_aa80d968-4f91-4f00-b5a1-a421174f5a60_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_aa80d968-4f91-4f00-b5a1-a421174f5a60" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_aa80d968-4f91-4f00-b5a1-a421174f5a60_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_e0a87a9f-8b75-46c7-b55a-30fc49854cae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_aa80d968-4f91-4f00-b5a1-a421174f5a60" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_e0a87a9f-8b75-46c7-b55a-30fc49854cae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashMember_ef9a1d52-df7e-4dc6-a868-a80bcaf2938b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_e0a87a9f-8b75-46c7-b55a-30fc49854cae" xlink:to="loc_us-gaap_CashMember_ef9a1d52-df7e-4dc6-a868-a80bcaf2938b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_a0c5fe69-755e-483a-861f-87a9cf45ffd6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_e0a87a9f-8b75-46c7-b55a-30fc49854cae" xlink:to="loc_us-gaap_MoneyMarketFundsMember_a0c5fe69-755e-483a-861f-87a9cf45ffd6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_331c8389-f7bb-4316-8792-fd68e26fbc35" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4e4e2e10-5e25-4643-89c3-022b6041ffb9" xlink:to="loc_us-gaap_FinancialInstrumentAxis_331c8389-f7bb-4316-8792-fd68e26fbc35" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_331c8389-f7bb-4316-8792-fd68e26fbc35_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_331c8389-f7bb-4316-8792-fd68e26fbc35" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_331c8389-f7bb-4316-8792-fd68e26fbc35_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ef6623ea-260f-4774-910f-1c54ca0446c9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_331c8389-f7bb-4316-8792-fd68e26fbc35" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ef6623ea-260f-4774-910f-1c54ca0446c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_f6866bd0-8c4b-4c9e-8773-a6bbe60793da" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ef6623ea-260f-4774-910f-1c54ca0446c9" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_f6866bd0-8c4b-4c9e-8773-a6bbe60793da" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MunicipalDebtSecuritiesMember_b49d6652-40da-42f8-9cfe-d64398b042d0" xlink:href="supn-20241231.xsd#supn_MunicipalDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ef6623ea-260f-4774-910f-1c54ca0446c9" xlink:to="loc_supn_MunicipalDebtSecuritiesMember_b49d6652-40da-42f8-9cfe-d64398b042d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_7c4faa97-193a-4a63-8c09-7129d8d68418" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ef6623ea-260f-4774-910f-1c54ca0446c9" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_7c4faa97-193a-4a63-8c09-7129d8d68418" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_15f37531-664a-467c-bb7f-d9e6b9dcfce9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2b847ef5-3275-4526-a936-f068b85708c1" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_15f37531-664a-467c-bb7f-d9e6b9dcfce9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_309d5eb1-d269-4fa0-83b0-a10c055a0c41" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_15f37531-664a-467c-bb7f-d9e6b9dcfce9" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_309d5eb1-d269-4fa0-83b0-a10c055a0c41" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesCurrentAbstract_3e19e2c7-6ace-4d69-a735-f5bbec88f1dc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesCurrentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_15f37531-664a-467c-bb7f-d9e6b9dcfce9" xlink:to="loc_us-gaap_DebtSecuritiesCurrentAbstract_3e19e2c7-6ace-4d69-a735-f5bbec88f1dc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_9a685bc3-445e-46fd-a348-331216b56d4d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtSecuritiesCurrentAbstract_3e19e2c7-6ace-4d69-a735-f5bbec88f1dc" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_9a685bc3-445e-46fd-a348-331216b56d4d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_d6e7499a-40ed-4ec3-b293-08af37702159" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtSecuritiesCurrentAbstract_3e19e2c7-6ace-4d69-a735-f5bbec88f1dc" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_d6e7499a-40ed-4ec3-b293-08af37702159" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrentAbstract_28a7784f-dc47-46d2-8370-1424675ad9f2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsNoncurrentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_15f37531-664a-467c-bb7f-d9e6b9dcfce9" xlink:to="loc_us-gaap_OtherAssetsNoncurrentAbstract_28a7784f-dc47-46d2-8370-1424675ad9f2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanAssetsForPlanBenefitsNoncurrent_9ddc7a45-01ea-4491-98d1-e7dd838337ad" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedBenefitPlanAssetsForPlanBenefitsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherAssetsNoncurrentAbstract_28a7784f-dc47-46d2-8370-1424675ad9f2" xlink:to="loc_us-gaap_DefinedBenefitPlanAssetsForPlanBenefitsNoncurrent_9ddc7a45-01ea-4491-98d1-e7dd838337ad" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_a217a567-120a-4a52-a95d-bcec8d408f33" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_15f37531-664a-467c-bb7f-d9e6b9dcfce9" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_a217a567-120a-4a52-a95d-bcec8d408f33" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_5f548418-0f0f-41af-a150-1285cf2feb31" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2b847ef5-3275-4526-a936-f068b85708c1" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_5f548418-0f0f-41af-a150-1285cf2feb31" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_1061987f-7a04-43d1-b1b8-48812f2cd0f6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_5f548418-0f0f-41af-a150-1285cf2feb31" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_1061987f-7a04-43d1-b1b8-48812f2cd0f6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_9c1cab15-3ec4-4bc2-80c0-d468a4e4d175" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_5f548418-0f0f-41af-a150-1285cf2feb31" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosure_9c1cab15-3ec4-4bc2-80c0-d468a4e4d175" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ContingentConsiderationNarrativeDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#ContingentConsiderationNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ContingentConsiderationNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_b8830c36-3020-4a6d-ae8d-a6326b589ab7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_b8830c36-3020-4a6d-ae8d-a6326b589ab7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_bc40d04c-f5cc-449c-bc04-61b88075d797" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_b8830c36-3020-4a6d-ae8d-a6326b589ab7" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_bc40d04c-f5cc-449c-bc04-61b88075d797" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_bc40d04c-f5cc-449c-bc04-61b88075d797_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_bc40d04c-f5cc-449c-bc04-61b88075d797" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_bc40d04c-f5cc-449c-bc04-61b88075d797_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_e233eae6-d6ca-47d6-8150-646246d20ec9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_bc40d04c-f5cc-449c-bc04-61b88075d797" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_e233eae6-d6ca-47d6-8150-646246d20ec9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_f543bc57-589a-4ed9-b5c6-6de59defe830" xlink:href="supn-20241231.xsd#supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_e233eae6-d6ca-47d6-8150-646246d20ec9" xlink:to="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_f543bc57-589a-4ed9-b5c6-6de59defe830" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_AdamasMember_b7ec8b05-c05c-4819-a886-cf10791fa5e7" xlink:href="supn-20241231.xsd#supn_AdamasMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_e233eae6-d6ca-47d6-8150-646246d20ec9" xlink:to="loc_supn_AdamasMember_b7ec8b05-c05c-4819-a886-cf10791fa5e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationByTypeAxis_66a15dd8-5501-43ef-bc29-4b779d0ed87e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContingentConsiderationByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_b8830c36-3020-4a6d-ae8d-a6326b589ab7" xlink:to="loc_us-gaap_ContingentConsiderationByTypeAxis_66a15dd8-5501-43ef-bc29-4b779d0ed87e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_66a15dd8-5501-43ef-bc29-4b779d0ed87e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_66a15dd8-5501-43ef-bc29-4b779d0ed87e" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_66a15dd8-5501-43ef-bc29-4b779d0ed87e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_9b214e6b-e9ec-404f-8e2e-a18d89648e01" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_66a15dd8-5501-43ef-bc29-4b779d0ed87e" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_9b214e6b-e9ec-404f-8e2e-a18d89648e01" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_SPN830RegulatoryAndCommercialActivitiesMember_a206e50c-a17a-4688-9aaf-6857dedee6ac" xlink:href="supn-20241231.xsd#supn_SPN830RegulatoryAndCommercialActivitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_9b214e6b-e9ec-404f-8e2e-a18d89648e01" xlink:to="loc_supn_SPN830RegulatoryAndCommercialActivitiesMember_a206e50c-a17a-4688-9aaf-6857dedee6ac" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_SPN830NDAApprovalMilestoneMember_57d76ebe-aeb0-4594-b492-1de14296bac6" xlink:href="supn-20241231.xsd#supn_SPN830NDAApprovalMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_9b214e6b-e9ec-404f-8e2e-a18d89648e01" xlink:to="loc_supn_SPN830NDAApprovalMilestoneMember_57d76ebe-aeb0-4594-b492-1de14296bac6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_SubsequentCommercialProductLaunchMember_f9fcaf28-698a-4bfa-ab50-7fad8051ca61" xlink:href="supn-20241231.xsd#supn_SubsequentCommercialProductLaunchMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_9b214e6b-e9ec-404f-8e2e-a18d89648e01" xlink:to="loc_supn_SubsequentCommercialProductLaunchMember_f9fcaf28-698a-4bfa-ab50-7fad8051ca61" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_Milestone2024Member_867060f9-f966-4555-9aa8-f3c6f38707e8" xlink:href="supn-20241231.xsd#supn_Milestone2024Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_9b214e6b-e9ec-404f-8e2e-a18d89648e01" xlink:to="loc_supn_Milestone2024Member_867060f9-f966-4555-9aa8-f3c6f38707e8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_Milestone2024AndMilestone2025Member_d12b427a-1e2b-4c2f-b195-fc91fe0cff7a" xlink:href="supn-20241231.xsd#supn_Milestone2024AndMilestone2025Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_9b214e6b-e9ec-404f-8e2e-a18d89648e01" xlink:to="loc_supn_Milestone2024AndMilestone2025Member_d12b427a-1e2b-4c2f-b195-fc91fe0cff7a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh_9cbfc954-519c-4ede-88b2-992b28461a52" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh_9cbfc954-519c-4ede-88b2-992b28461a52" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_BusinessCombinationContingentConsiderationNumberOfContingentValueRightsPerCommonShare_e81630cc-1183-4ed5-9b3f-fad75665d03b" xlink:href="supn-20241231.xsd#supn_BusinessCombinationContingentConsiderationNumberOfContingentValueRightsPerCommonShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_supn_BusinessCombinationContingentConsiderationNumberOfContingentValueRightsPerCommonShare_e81630cc-1183-4ed5-9b3f-fad75665d03b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_BusinessCombinationContingentConsiderationArrangementsValuePricePerShare_cf8b0dd3-0e21-40a1-af6f-93706e06804d" xlink:href="supn-20241231.xsd#supn_BusinessCombinationContingentConsiderationArrangementsValuePricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_supn_BusinessCombinationContingentConsiderationArrangementsValuePricePerShare_cf8b0dd3-0e21-40a1-af6f-93706e06804d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationExcessAcquisitionDateFairValue_1ac76759-75a6-4f4a-b29d-44e7ae351d42" xlink:href="supn-20241231.xsd#supn_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationExcessAcquisitionDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_supn_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationExcessAcquisitionDateFairValue_1ac76759-75a6-4f4a-b29d-44e7ae351d42" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationExcessAcquisitionDateFairValueTerm_9f782f73-668b-48c9-90cb-8c9607bdf4ae" xlink:href="supn-20241231.xsd#supn_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationExcessAcquisitionDateFairValueTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_supn_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationExcessAcquisitionDateFairValueTerm_9f782f73-668b-48c9-90cb-8c9607bdf4ae" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueLow_a25595a0-d26d-4703-aabe-36a93880fa1f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueLow"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueLow_a25595a0-d26d-4703-aabe-36a93880fa1f" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_9284f990-b30a-4c20-9788-1b0e983824ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_9284f990-b30a-4c20-9788-1b0e983824ba" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements_9076315d-0ae9-4b05-a8f3-1e09e33878cb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements_9076315d-0ae9-4b05-a8f3-1e09e33878cb" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities_90936b67-116f-4853-952a-1a2d3311aa55" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities_90936b67-116f-4853-952a-1a2d3311aa55" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities_4d6d0842-28e4-4bce-b964-8879ad9fb5bb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_91eaa416-b97a-492a-a7d2-76ac61b42fa3" xlink:to="loc_us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities_4d6d0842-28e4-4bce-b964-8879ad9fb5bb" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ContingentConsiderationReconciliationoftheBeginningandEndingBalancesRelatedtotheContingentConsiderationDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#ContingentConsiderationReconciliationoftheBeginningandEndingBalancesRelatedtotheContingentConsiderationDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ContingentConsiderationReconciliationoftheBeginningandEndingBalancesRelatedtotheContingentConsiderationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a87d9eb8-c24c-48b8-9ae2-7e53b9448194" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_fb956159-8ec5-4d7a-83e1-1e32f6541397" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a87d9eb8-c24c-48b8-9ae2-7e53b9448194" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_fb956159-8ec5-4d7a-83e1-1e32f6541397" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_e333cb77-cff7-445b-9a57-a8be59558306" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_fb956159-8ec5-4d7a-83e1-1e32f6541397" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_e333cb77-cff7-445b-9a57-a8be59558306" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_e333cb77-cff7-445b-9a57-a8be59558306_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_e333cb77-cff7-445b-9a57-a8be59558306" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_e333cb77-cff7-445b-9a57-a8be59558306_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_25396c05-40ca-4b37-94d9-6eb68c1c4079" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_e333cb77-cff7-445b-9a57-a8be59558306" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_25396c05-40ca-4b37-94d9-6eb68c1c4079" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_11ebdb0f-6b32-4b64-a04d-a228d3cd948b" xlink:href="supn-20241231.xsd#supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_25396c05-40ca-4b37-94d9-6eb68c1c4079" xlink:to="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_11ebdb0f-6b32-4b64-a04d-a228d3cd948b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_AdamasMember_9b2ad9b1-1d23-4f39-9d7e-3d70cf82bc3d" xlink:href="supn-20241231.xsd#supn_AdamasMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_25396c05-40ca-4b37-94d9-6eb68c1c4079" xlink:to="loc_supn_AdamasMember_9b2ad9b1-1d23-4f39-9d7e-3d70cf82bc3d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputReconciliationRollForward_d1dc1cb6-6632-41fb-89e2-0f41e61a30da" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputReconciliationRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a87d9eb8-c24c-48b8-9ae2-7e53b9448194" xlink:to="loc_us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputReconciliationRollForward_d1dc1cb6-6632-41fb-89e2-0f41e61a30da" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_95de85b8-aebf-4fec-ab09-fe89197d6e7e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputReconciliationRollForward_d1dc1cb6-6632-41fb-89e2-0f41e61a30da" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_95de85b8-aebf-4fec-ab09-fe89197d6e7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements_f0422736-0f62-4082-9422-6ef44014b3fd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputReconciliationRollForward_d1dc1cb6-6632-41fb-89e2-0f41e61a30da" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements_f0422736-0f62-4082-9422-6ef44014b3fd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_215b2141-fa86-4bbe-89ce-6564bc9914e2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueNetDerivativeAssetLiabilityMeasuredOnRecurringBasisUnobservableInputReconciliationRollForward_d1dc1cb6-6632-41fb-89e2-0f41e61a30da" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_215b2141-fa86-4bbe-89ce-6564bc9914e2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueRecurringBasisUnobservableInputReconciliationLiabilityGainLossStatementOfIncomeExtensibleList_f9edc537-beb0-49f5-a80f-8419fd17cf27" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueRecurringBasisUnobservableInputReconciliationLiabilityGainLossStatementOfIncomeExtensibleList"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_215b2141-fa86-4bbe-89ce-6564bc9914e2" xlink:to="loc_us-gaap_FairValueRecurringBasisUnobservableInputReconciliationLiabilityGainLossStatementOfIncomeExtensibleList_f9edc537-beb0-49f5-a80f-8419fd17cf27" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_324661a9-19e2-43aa-bfd1-58662ec1e47b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/GoodwillandIntangibleAssetsNetScheduleofIntangibleAssetsGrossCarryingAmountandRelatedAccumulatedAmortizationDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#GoodwillandIntangibleAssetsNetScheduleofIntangibleAssetsGrossCarryingAmountandRelatedAccumulatedAmortizationDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/GoodwillandIntangibleAssetsNetScheduleofIntangibleAssetsGrossCarryingAmountandRelatedAccumulatedAmortizationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassLineItems_cd50f037-e3ae-4da8-82a0-00c4870f8a97" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfIndefiniteLivedIntangibleAssetsTable_cbdb99a3-680c-44ee-bb65-b9f1b98db309" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfIndefiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassLineItems_cd50f037-e3ae-4da8-82a0-00c4870f8a97" xlink:to="loc_us-gaap_ScheduleOfIndefiniteLivedIntangibleAssetsTable_cbdb99a3-680c-44ee-bb65-b9f1b98db309" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_0fa3f991-0334-444d-98f5-6334308c7fbb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfIndefiniteLivedIntangibleAssetsTable_cbdb99a3-680c-44ee-bb65-b9f1b98db309" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_0fa3f991-0334-444d-98f5-6334308c7fbb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_0fa3f991-0334-444d-98f5-6334308c7fbb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_0fa3f991-0334-444d-98f5-6334308c7fbb" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_0fa3f991-0334-444d-98f5-6334308c7fbb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_6fc4f4ac-b616-4a37-a03d-32701838900d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_0fa3f991-0334-444d-98f5-6334308c7fbb" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_6fc4f4ac-b616-4a37-a03d-32701838900d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_e59c0395-299a-4d8b-a34c-71fce0cefb5f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_6fc4f4ac-b616-4a37-a03d-32701838900d" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_e59c0395-299a-4d8b-a34c-71fce0cefb5f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill_08f22197-fa8c-4319-8f29-ddba34993139" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassLineItems_cd50f037-e3ae-4da8-82a0-00c4870f8a97" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill_08f22197-fa8c-4319-8f29-ddba34993139" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_93eda22f-77b5-4338-95ae-ee1dcf74360e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_f8c0d471-a301-479a-b358-a3ce4fd1e330" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_93eda22f-77b5-4338-95ae-ee1dcf74360e" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_f8c0d471-a301-479a-b358-a3ce4fd1e330" xlink:type="arc" order="2" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_94bca4c4-7793-4c1d-9930-a9efc6827d87" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_f8c0d471-a301-479a-b358-a3ce4fd1e330" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_94bca4c4-7793-4c1d-9930-a9efc6827d87" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_94bca4c4-7793-4c1d-9930-a9efc6827d87_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_94bca4c4-7793-4c1d-9930-a9efc6827d87" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_94bca4c4-7793-4c1d-9930-a9efc6827d87_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_b6187693-7d45-4c30-ad05-80e3eb5cc8f3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_94bca4c4-7793-4c1d-9930-a9efc6827d87" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_b6187693-7d45-4c30-ad05-80e3eb5cc8f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DevelopedTechnologyRightsMember_b4683777-7b0e-49e7-9e79-fb356b00b75b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DevelopedTechnologyRightsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_b6187693-7d45-4c30-ad05-80e3eb5cc8f3" xlink:to="loc_us-gaap_DevelopedTechnologyRightsMember_b4683777-7b0e-49e7-9e79-fb356b00b75b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_PatentDefenseCostsMember_b87de308-3ec6-4304-be02-8e2325a36f4a" xlink:href="supn-20241231.xsd#supn_PatentDefenseCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_b6187693-7d45-4c30-ad05-80e3eb5cc8f3" xlink:to="loc_supn_PatentDefenseCostsMember_b87de308-3ec6-4304-be02-8e2325a36f4a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsRemainingAmortizationPeriod1_bd01df94-acfa-4d73-85b8-a5f5f70bf992" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsRemainingAmortizationPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_93eda22f-77b5-4338-95ae-ee1dcf74360e" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsRemainingAmortizationPeriod1_bd01df94-acfa-4d73-85b8-a5f5f70bf992" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_c7a7d98d-6853-4257-ad54-3e398660f249" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_93eda22f-77b5-4338-95ae-ee1dcf74360e" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_c7a7d98d-6853-4257-ad54-3e398660f249" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_c808323f-f654-42b4-8599-0141ea51ed9c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_93eda22f-77b5-4338-95ae-ee1dcf74360e" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_c808323f-f654-42b4-8599-0141ea51ed9c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_dd81d1cd-c638-40b3-ba3a-c6ad5be55d62" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_93eda22f-77b5-4338-95ae-ee1dcf74360e" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_dd81d1cd-c638-40b3-ba3a-c6ad5be55d62" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/DebtDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#DebtDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/DebtDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_bc8afbbf-4a67-4cdd-b36c-aac9b0adbe91" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_DebtInstrumentTable_bc8afbbf-4a67-4cdd-b36c-aac9b0adbe91" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_f459db4e-07ea-4d74-877f-112dd7e0ff43" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bc8afbbf-4a67-4cdd-b36c-aac9b0adbe91" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_f459db4e-07ea-4d74-877f-112dd7e0ff43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_f459db4e-07ea-4d74-877f-112dd7e0ff43_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_f459db4e-07ea-4d74-877f-112dd7e0ff43" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_f459db4e-07ea-4d74-877f-112dd7e0ff43_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_b36137bd-ae88-48a9-9c24-6c5d51d98614" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_f459db4e-07ea-4d74-877f-112dd7e0ff43" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_b36137bd-ae88-48a9-9c24-6c5d51d98614" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_8d48fc26-a6e7-4fd9-8e4c-4c131d28f1e8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_b36137bd-ae88-48a9-9c24-6c5d51d98614" xlink:to="loc_us-gaap_ConvertibleDebtMember_8d48fc26-a6e7-4fd9-8e4c-4c131d28f1e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtTypeAxis_9352698a-4b03-4743-a823-e722342f0926" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShortTermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bc8afbbf-4a67-4cdd-b36c-aac9b0adbe91" xlink:to="loc_us-gaap_ShortTermDebtTypeAxis_9352698a-4b03-4743-a823-e722342f0926" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtTypeDomain_9352698a-4b03-4743-a823-e722342f0926_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShortTermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ShortTermDebtTypeAxis_9352698a-4b03-4743-a823-e722342f0926" xlink:to="loc_us-gaap_ShortTermDebtTypeDomain_9352698a-4b03-4743-a823-e722342f0926_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtTypeDomain_fd532cb3-ad02-4217-bf27-eda6ce6c3679" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShortTermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ShortTermDebtTypeAxis_9352698a-4b03-4743-a823-e722342f0926" xlink:to="loc_us-gaap_ShortTermDebtTypeDomain_fd532cb3-ad02-4217-bf27-eda6ce6c3679" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_0702c796-9d0a-46ee-bd17-2053a6b50280" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShortTermDebtTypeDomain_fd532cb3-ad02-4217-bf27-eda6ce6c3679" xlink:to="loc_us-gaap_ConvertibleDebtMember_0702c796-9d0a-46ee-bd17-2053a6b50280" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_833dbbe7-d5c5-432f-bd57-a3926af0b17e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShortTermDebtTypeDomain_fd532cb3-ad02-4217-bf27-eda6ce6c3679" xlink:to="loc_us-gaap_LineOfCreditMember_833dbbe7-d5c5-432f-bd57-a3926af0b17e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_fab7f5e1-1216-479b-a40b-4f41ad4aacc0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bc8afbbf-4a67-4cdd-b36c-aac9b0adbe91" xlink:to="loc_us-gaap_CreditFacilityAxis_fab7f5e1-1216-479b-a40b-4f41ad4aacc0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_fab7f5e1-1216-479b-a40b-4f41ad4aacc0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_fab7f5e1-1216-479b-a40b-4f41ad4aacc0" xlink:to="loc_us-gaap_CreditFacilityDomain_fab7f5e1-1216-479b-a40b-4f41ad4aacc0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_06b64377-ff7e-44c4-81d0-cf4ddd090230" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_fab7f5e1-1216-479b-a40b-4f41ad4aacc0" xlink:to="loc_us-gaap_CreditFacilityDomain_06b64377-ff7e-44c4-81d0-cf4ddd090230" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevolvingCreditFacilityMember_4b50167f-9f80-4e4e-ad5e-983f9f7da1a0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevolvingCreditFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_06b64377-ff7e-44c4-81d0-cf4ddd090230" xlink:to="loc_us-gaap_RevolvingCreditFacilityMember_4b50167f-9f80-4e4e-ad5e-983f9f7da1a0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_44d20f75-6ac3-4a78-beff-e9c6f60b8992" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_44d20f75-6ac3-4a78-beff-e9c6f60b8992" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ExtinguishmentOfDebtAmount_38a7aa6b-b520-4243-8b02-4b4a129d11a1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ExtinguishmentOfDebtAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_ExtinguishmentOfDebtAmount_38a7aa6b-b520-4243-8b02-4b4a129d11a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestPaidNet_3ce37af3-4099-4bc6-989b-88f66aa20a18" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestPaidNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_InterestPaidNet_3ce37af3-4099-4bc6-989b-88f66aa20a18" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionOriginalDebtAmount1_7b1bc3fa-8ec2-4613-a258-30adf66670ee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtConversionOriginalDebtAmount1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_DebtConversionOriginalDebtAmount1_7b1bc3fa-8ec2-4613-a258-30adf66670ee" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentWarrantsOrOptionsIssued1_72d34f4f-7612-410f-bc32-2b7ce9dfd189" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtConversionConvertedInstrumentWarrantsOrOptionsIssued1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentWarrantsOrOptionsIssued1_72d34f4f-7612-410f-bc32-2b7ce9dfd189" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_dd4acc60-b0e9-462e-859c-de585a4ed01b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_dd4acc60-b0e9-462e-859c-de585a4ed01b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_ClassOfWarrantOrRightNumberOfSharesInWhichHolderCanBeEntitledPerWarrantsAtStrikePrice_017740de-f716-4573-ac71-c834e9dc4f2c" xlink:href="supn-20241231.xsd#supn_ClassOfWarrantOrRightNumberOfSharesInWhichHolderCanBeEntitledPerWarrantsAtStrikePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_supn_ClassOfWarrantOrRightNumberOfSharesInWhichHolderCanBeEntitledPerWarrantsAtStrikePrice_017740de-f716-4573-ac71-c834e9dc4f2c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_4fd3a9ba-6481-46b0-a1c5-78b841d3f2d3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_4fd3a9ba-6481-46b0-a1c5-78b841d3f2d3" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_563e0d70-64a6-4389-973a-c6cd07f5d07a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_563e0d70-64a6-4389-973a-c6cd07f5d07a" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfDebt_ffb8f047-ed67-4306-a901-7961496736b6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfDebt_ffb8f047-ed67-4306-a901-7961496736b6" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_f76ec181-434d-4485-8726-c8c3ab85462c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_InterestExpenseDebt_f76ec181-434d-4485-8726-c8c3ab85462c" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermBorrowings_6c8639ea-8ab6-4589-a044-eb8c24b19f36" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShortTermBorrowings"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_ee9fdad5-f8e4-466d-8902-26d4f8316523" xlink:to="loc_us-gaap_ShortTermBorrowings_6c8639ea-8ab6-4589-a044-eb8c24b19f36" xlink:type="arc" order="11"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ShareBasedPaymentsNarrativeDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#ShareBasedPaymentsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ShareBasedPaymentsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_03a03625-116c-41bd-ad4d-6be667eb36da" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_03a03625-116c-41bd-ad4d-6be667eb36da" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_7f18df65-ae2f-44bc-89dc-c10796bb7f05" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_03a03625-116c-41bd-ad4d-6be667eb36da" xlink:to="loc_us-gaap_PlanNameAxis_7f18df65-ae2f-44bc-89dc-c10796bb7f05" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_7f18df65-ae2f-44bc-89dc-c10796bb7f05_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_7f18df65-ae2f-44bc-89dc-c10796bb7f05" xlink:to="loc_us-gaap_PlanNameDomain_7f18df65-ae2f-44bc-89dc-c10796bb7f05_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_75cfd33c-50db-4de4-a558-d3994f0d1f83" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_7f18df65-ae2f-44bc-89dc-c10796bb7f05" xlink:to="loc_us-gaap_PlanNameDomain_75cfd33c-50db-4de4-a558-d3994f0d1f83" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_A2021EquityIncentivePlanMember_e595ec3b-89b6-4847-ae55-67dd58e92723" xlink:href="supn-20241231.xsd#supn_A2021EquityIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_75cfd33c-50db-4de4-a558-d3994f0d1f83" xlink:to="loc_supn_A2021EquityIncentivePlanMember_e595ec3b-89b6-4847-ae55-67dd58e92723" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_EquityIncentivePlan2012Member_2ddd6a65-4daa-4304-8d9e-7d4b3f45ee2d" xlink:href="supn-20241231.xsd#supn_EquityIncentivePlan2012Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_75cfd33c-50db-4de4-a558-d3994f0d1f83" xlink:to="loc_supn_EquityIncentivePlan2012Member_2ddd6a65-4daa-4304-8d9e-7d4b3f45ee2d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualAxis_5f303cd7-4b99-46bb-bc6f-06f617f3bc0f" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_TitleOfIndividualAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_03a03625-116c-41bd-ad4d-6be667eb36da" xlink:to="loc_srt_TitleOfIndividualAxis_5f303cd7-4b99-46bb-bc6f-06f617f3bc0f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_5f303cd7-4b99-46bb-bc6f-06f617f3bc0f_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_TitleOfIndividualAxis_5f303cd7-4b99-46bb-bc6f-06f617f3bc0f" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_5f303cd7-4b99-46bb-bc6f-06f617f3bc0f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_7f200c88-282d-42e8-823f-6beaa6898ece" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_TitleOfIndividualAxis_5f303cd7-4b99-46bb-bc6f-06f617f3bc0f" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_7f200c88-282d-42e8-823f-6beaa6898ece" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_EmployeesConsultantsAndAdvisorsMember_44562df5-13cd-4f8f-bd45-ca7d7de527e9" xlink:href="supn-20241231.xsd#supn_EmployeesConsultantsAndAdvisorsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_7f200c88-282d-42e8-823f-6beaa6898ece" xlink:to="loc_supn_EmployeesConsultantsAndAdvisorsMember_44562df5-13cd-4f8f-bd45-ca7d7de527e9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_DirectorMember_ce2ca7e6-5056-4e03-aaac-9c2c42942423" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_DirectorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_7f200c88-282d-42e8-823f-6beaa6898ece" xlink:to="loc_srt_DirectorMember_ce2ca7e6-5056-4e03-aaac-9c2c42942423" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_14820f9e-8c5d-40ad-80fa-ead94dbfc2c5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_03a03625-116c-41bd-ad4d-6be667eb36da" xlink:to="loc_us-gaap_AwardTypeAxis_14820f9e-8c5d-40ad-80fa-ead94dbfc2c5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_14820f9e-8c5d-40ad-80fa-ead94dbfc2c5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_14820f9e-8c5d-40ad-80fa-ead94dbfc2c5" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_14820f9e-8c5d-40ad-80fa-ead94dbfc2c5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_aa2d862a-a573-48f3-bd4c-feffb10589fe" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_14820f9e-8c5d-40ad-80fa-ead94dbfc2c5" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_aa2d862a-a573-48f3-bd4c-feffb10589fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_723ae0b3-4db6-442a-bece-2cd5559e4cd6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_aa2d862a-a573-48f3-bd4c-feffb10589fe" xlink:to="loc_us-gaap_EmployeeStockOptionMember_723ae0b3-4db6-442a-bece-2cd5559e4cd6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_ddd883a7-bba5-4e01-a695-7aee8e6b96c9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_aa2d862a-a573-48f3-bd4c-feffb10589fe" xlink:to="loc_us-gaap_EmployeeStockMember_ddd883a7-bba5-4e01-a695-7aee8e6b96c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_e1fbb122-adc8-47c0-beeb-7cf7ff00ae58" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_aa2d862a-a573-48f3-bd4c-feffb10589fe" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_e1fbb122-adc8-47c0-beeb-7cf7ff00ae58" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MarketBasedPerformanceSharesMember_ef524349-e917-4f57-a656-3b83f203668b" xlink:href="supn-20241231.xsd#supn_MarketBasedPerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_aa2d862a-a573-48f3-bd4c-feffb10589fe" xlink:to="loc_supn_MarketBasedPerformanceSharesMember_ef524349-e917-4f57-a656-3b83f203668b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_b48dd3e4-de37-43c5-b1f5-394dfba11782" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_aa2d862a-a573-48f3-bd4c-feffb10589fe" xlink:to="loc_us-gaap_PerformanceSharesMember_b48dd3e4-de37-43c5-b1f5-394dfba11782" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_VotesPerCommonShareNumber_be8f54a5-e4b9-4f8d-864d-d8abe8959354" xlink:href="supn-20241231.xsd#supn_VotesPerCommonShareNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_supn_VotesPerCommonShareNumber_be8f54a5-e4b9-4f8d-864d-d8abe8959354" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_f2c4c692-802a-4781-8115-c103db333855" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_f2c4c692-802a-4781-8115-c103db333855" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_9fa080b7-216d-497c-8a60-1739cbb3a485" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_9fa080b7-216d-497c-8a60-1739cbb3a485" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_e19d5e32-4b71-4e9a-8f75-1ebadcca23fb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_e19d5e32-4b71-4e9a-8f75-1ebadcca23fb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingNumberOfInstallmentsFromFirstAnniversaryOfGrantDate_539e6662-aca7-4a37-ac8c-b19209e56e60" xlink:href="supn-20241231.xsd#supn_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingNumberOfInstallmentsFromFirstAnniversaryOfGrantDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_supn_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingNumberOfInstallmentsFromFirstAnniversaryOfGrantDate_539e6662-aca7-4a37-ac8c-b19209e56e60" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_a2d95a86-b13c-436f-ad46-14424df9bbbe" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_a2d95a86-b13c-436f-ad46-14424df9bbbe" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_0a46b258-d368-4264-a3ea-dbd29af105a7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_0a46b258-d368-4264-a3ea-dbd29af105a7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_40452a3b-57ad-4e5d-beca-0711ecb6c290" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_40452a3b-57ad-4e5d-beca-0711ecb6c290" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_66cc8cee-e21e-4835-aa17-9b3c0d3e335a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_66cc8cee-e21e-4835-aa17-9b3c0d3e335a" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_50e2fcbe-cb63-4f55-8454-478704055809" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_50e2fcbe-cb63-4f55-8454-478704055809" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_92af76d9-48a8-4814-ab18-8092a6659fc5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_92af76d9-48a8-4814-ab18-8092a6659fc5" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_ac3bb5ab-8fa9-4b7b-95d3-5f6b06ed8d4a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_ac3bb5ab-8fa9-4b7b-95d3-5f6b06ed8d4a" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_c2f7794a-74db-4916-b4c4-d5a523d2d8b7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_c2f7794a-74db-4916-b4c4-d5a523d2d8b7" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_02533c32-b9b9-48cc-a5dd-cb5fffdead1d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_93e19ca5-9fb3-4dd5-8691-514702a7d92f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_02533c32-b9b9-48cc-a5dd-cb5fffdead1d" xlink:type="arc" order="13"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ShareBasedPaymentsSharebasedCompensationExpenseDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#ShareBasedPaymentsSharebasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ShareBasedPaymentsSharebasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_c6d57c22-a8a1-4627-8503-c9b159d81f13" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_279dc740-d21b-4164-891a-1e4a268e615c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_c6d57c22-a8a1-4627-8503-c9b159d81f13" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_279dc740-d21b-4164-891a-1e4a268e615c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_2fd1bad9-7a84-4157-89ac-423fa4a66c4d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_279dc740-d21b-4164-891a-1e4a268e615c" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_2fd1bad9-7a84-4157-89ac-423fa4a66c4d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_2fd1bad9-7a84-4157-89ac-423fa4a66c4d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_2fd1bad9-7a84-4157-89ac-423fa4a66c4d" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_2fd1bad9-7a84-4157-89ac-423fa4a66c4d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_52f040b0-ece3-4318-8a56-961293d7a781" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_2fd1bad9-7a84-4157-89ac-423fa4a66c4d" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_52f040b0-ece3-4318-8a56-961293d7a781" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_21c09c39-9358-4592-952e-b2d2ee85c702" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_52f040b0-ece3-4318-8a56-961293d7a781" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_21c09c39-9358-4592-952e-b2d2ee85c702" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_37d36907-711f-4c02-bd15-67edfd5aa3e3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_52f040b0-ece3-4318-8a56-961293d7a781" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_37d36907-711f-4c02-bd15-67edfd5aa3e3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_73d5175d-d911-46dd-bf12-5a4977c4c442" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_c6d57c22-a8a1-4627-8503-c9b159d81f13" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_73d5175d-d911-46dd-bf12-5a4977c4c442" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ShareBasedPaymentsFairValueofEachOptionAwardedDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#ShareBasedPaymentsFairValueofEachOptionAwardedDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ShareBasedPaymentsFairValueofEachOptionAwardedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0c91826e-4c63-4794-838b-6885b8a0a66c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0c91826e-4c63-4794-838b-6885b8a0a66c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_204df13e-133b-4ca3-864d-f693e7580963" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0c91826e-4c63-4794-838b-6885b8a0a66c" xlink:to="loc_us-gaap_AwardTypeAxis_204df13e-133b-4ca3-864d-f693e7580963" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_204df13e-133b-4ca3-864d-f693e7580963_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_204df13e-133b-4ca3-864d-f693e7580963" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_204df13e-133b-4ca3-864d-f693e7580963_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_00472d8f-cbdf-4b2f-b84e-a5ba20e75322" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_204df13e-133b-4ca3-864d-f693e7580963" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_00472d8f-cbdf-4b2f-b84e-a5ba20e75322" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_85bbcbfb-6e9d-459f-a234-7666fe90410b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_00472d8f-cbdf-4b2f-b84e-a5ba20e75322" xlink:to="loc_us-gaap_EmployeeStockOptionMember_85bbcbfb-6e9d-459f-a234-7666fe90410b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_823a8a9e-d96e-419d-ae6e-3c3f232e4538" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0c91826e-4c63-4794-838b-6885b8a0a66c" xlink:to="loc_srt_RangeAxis_823a8a9e-d96e-419d-ae6e-3c3f232e4538" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_823a8a9e-d96e-419d-ae6e-3c3f232e4538_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_823a8a9e-d96e-419d-ae6e-3c3f232e4538" xlink:to="loc_srt_RangeMember_823a8a9e-d96e-419d-ae6e-3c3f232e4538_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_fa6e63b9-1b15-45b7-85e3-b31648a440d2" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_823a8a9e-d96e-419d-ae6e-3c3f232e4538" xlink:to="loc_srt_RangeMember_fa6e63b9-1b15-45b7-85e3-b31648a440d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_e9a47d9a-9d64-40f0-8502-2203bde7f10a" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_fa6e63b9-1b15-45b7-85e3-b31648a440d2" xlink:to="loc_srt_MinimumMember_e9a47d9a-9d64-40f0-8502-2203bde7f10a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_4ac26002-c417-4b47-9ec2-f2849c34b27d" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_fa6e63b9-1b15-45b7-85e3-b31648a440d2" xlink:to="loc_srt_MaximumMember_4ac26002-c417-4b47-9ec2-f2849c34b27d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharePrice_fa154cd3-888b-4abe-a81e-5adf308d151c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_SharePrice_fa154cd3-888b-4abe-a81e-5adf308d151c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_c153b93d-5570-41d6-8cfe-3f996634fee0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_c153b93d-5570-41d6-8cfe-3f996634fee0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_02e24534-fd2f-434e-9197-9f3fda30c808" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_02e24534-fd2f-434e-9197-9f3fda30c808" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_317bacb0-c4e0-4c05-b7b0-a282871e9242" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_317bacb0-c4e0-4c05-b7b0-a282871e9242" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_d0a1b728-b1d1-47fd-bf2d-ffeca1b6593c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_d0a1b728-b1d1-47fd-bf2d-ffeca1b6593c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_55b7ec43-4060-43fe-8c4b-63db7290d448" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_55b7ec43-4060-43fe-8c4b-63db7290d448" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_b39e9a7d-f5af-4126-bc32-927c7625f6ae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5ec6204a-d204-4489-86fd-f4d402cb4d8d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_b39e9a7d-f5af-4126-bc32-927c7625f6ae" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ShareBasedPaymentsRestrictedStockUnitsDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#ShareBasedPaymentsRestrictedStockUnitsDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ShareBasedPaymentsRestrictedStockUnitsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_943cf3fd-2e40-4c38-8edc-25c1c5943a1b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_4f9a2203-70ce-4902-9379-d64511ca0acc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_943cf3fd-2e40-4c38-8edc-25c1c5943a1b" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_4f9a2203-70ce-4902-9379-d64511ca0acc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_efaedb6b-fb5f-4609-8e11-aabbdc524b60" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_4f9a2203-70ce-4902-9379-d64511ca0acc" xlink:to="loc_us-gaap_AwardTypeAxis_efaedb6b-fb5f-4609-8e11-aabbdc524b60" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_efaedb6b-fb5f-4609-8e11-aabbdc524b60_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_efaedb6b-fb5f-4609-8e11-aabbdc524b60" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_efaedb6b-fb5f-4609-8e11-aabbdc524b60_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_48cec8cc-eafb-4578-baf7-29ec3d138eeb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_efaedb6b-fb5f-4609-8e11-aabbdc524b60" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_48cec8cc-eafb-4578-baf7-29ec3d138eeb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_d5f34be9-c811-4434-b102-cc887753be33" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_48cec8cc-eafb-4578-baf7-29ec3d138eeb" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_d5f34be9-c811-4434-b102-cc887753be33" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_4342fd62-4518-4758-ad42-eef7e715e752" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_943cf3fd-2e40-4c38-8edc-25c1c5943a1b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_4342fd62-4518-4758-ad42-eef7e715e752" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_7973a534-9302-4fff-9bee-54ea8e3e11d3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_4342fd62-4518-4758-ad42-eef7e715e752" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_7973a534-9302-4fff-9bee-54ea8e3e11d3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_f0c2f990-86d6-42e2-91a0-488d7b21f023" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_4342fd62-4518-4758-ad42-eef7e715e752" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_f0c2f990-86d6-42e2-91a0-488d7b21f023" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_6380b300-0283-4ef3-97d1-2f744fa01363" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_4342fd62-4518-4758-ad42-eef7e715e752" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_6380b300-0283-4ef3-97d1-2f744fa01363" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_25a5026c-6b96-492a-9aae-308b14c89534" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_4342fd62-4518-4758-ad42-eef7e715e752" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_25a5026c-6b96-492a-9aae-308b14c89534" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_7cf73c7e-9a78-446c-932d-065b019406f3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_8d4a2bb9-57fe-4269-b3ad-c996625d2f87" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_943cf3fd-2e40-4c38-8edc-25c1c5943a1b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_8d4a2bb9-57fe-4269-b3ad-c996625d2f87" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_a9feb18c-b66d-4555-9418-be4d5f48dddb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_8d4a2bb9-57fe-4269-b3ad-c996625d2f87" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_a9feb18c-b66d-4555-9418-be4d5f48dddb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_464857ab-b625-4777-8424-c5af83e69d3c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_8d4a2bb9-57fe-4269-b3ad-c996625d2f87" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_464857ab-b625-4777-8424-c5af83e69d3c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_c1931447-a761-4d58-844e-ea361e8115ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_8d4a2bb9-57fe-4269-b3ad-c996625d2f87" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_c1931447-a761-4d58-844e-ea361e8115ba" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_9b646d1f-5602-4c1d-bc65-5ead831b6f11" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_8d4a2bb9-57fe-4269-b3ad-c996625d2f87" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_9b646d1f-5602-4c1d-bc65-5ead831b6f11" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_e3af644c-9089-490a-ba3c-1db41e01f73e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/ShareBasedPaymentsPerformanceStockUnitsDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#ShareBasedPaymentsPerformanceStockUnitsDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/ShareBasedPaymentsPerformanceStockUnitsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7a4c7cc9-1357-4fd6-9e45-ae31d03eba91" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e52d9330-c606-4098-a6b8-1d63cf6fb4f5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7a4c7cc9-1357-4fd6-9e45-ae31d03eba91" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e52d9330-c606-4098-a6b8-1d63cf6fb4f5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_9fcaf802-a701-4ce6-af5e-4496429bab22" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e52d9330-c606-4098-a6b8-1d63cf6fb4f5" xlink:to="loc_us-gaap_AwardTypeAxis_9fcaf802-a701-4ce6-af5e-4496429bab22" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_9fcaf802-a701-4ce6-af5e-4496429bab22_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_9fcaf802-a701-4ce6-af5e-4496429bab22" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_9fcaf802-a701-4ce6-af5e-4496429bab22_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e7874db5-6a33-4a82-8daa-31fa42c8f231" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_9fcaf802-a701-4ce6-af5e-4496429bab22" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e7874db5-6a33-4a82-8daa-31fa42c8f231" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_672d86b4-73b6-4980-9197-4360629dde6d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e7874db5-6a33-4a82-8daa-31fa42c8f231" xlink:to="loc_us-gaap_PerformanceSharesMember_672d86b4-73b6-4980-9197-4360629dde6d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_PerformanceBasedUnitsMember_000db1eb-22c6-4289-8911-12debe92066d" xlink:href="supn-20241231.xsd#supn_PerformanceBasedUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PerformanceSharesMember_672d86b4-73b6-4980-9197-4360629dde6d" xlink:to="loc_supn_PerformanceBasedUnitsMember_000db1eb-22c6-4289-8911-12debe92066d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MarketBasedUnitsMember_885e447e-6a04-4f73-b071-7d7f66dc03fc" xlink:href="supn-20241231.xsd#supn_MarketBasedUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PerformanceSharesMember_672d86b4-73b6-4980-9197-4360629dde6d" xlink:to="loc_supn_MarketBasedUnitsMember_885e447e-6a04-4f73-b071-7d7f66dc03fc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fb80eaf-1fe5-4391-a4e0-24c2919c2860" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7a4c7cc9-1357-4fd6-9e45-ae31d03eba91" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fb80eaf-1fe5-4391-a4e0-24c2919c2860" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d6ce44e5-576a-49e8-b670-2a2b2917ac3a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fb80eaf-1fe5-4391-a4e0-24c2919c2860" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d6ce44e5-576a-49e8-b670-2a2b2917ac3a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_271fc61d-0a37-4dc9-83a0-b5ebdc93a979" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fb80eaf-1fe5-4391-a4e0-24c2919c2860" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_271fc61d-0a37-4dc9-83a0-b5ebdc93a979" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_58fd3ebb-6c50-4313-b9c8-713bd13eba25" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fb80eaf-1fe5-4391-a4e0-24c2919c2860" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_58fd3ebb-6c50-4313-b9c8-713bd13eba25" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_e8683fb4-1830-4372-a441-e681722f12a4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fb80eaf-1fe5-4391-a4e0-24c2919c2860" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_e8683fb4-1830-4372-a441-e681722f12a4" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_04215468-15ab-430e-ad20-0fb22522021c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_dd618753-0a54-4386-b684-12206b98672e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7a4c7cc9-1357-4fd6-9e45-ae31d03eba91" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_dd618753-0a54-4386-b684-12206b98672e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_17c3f530-8ebd-40a8-b034-9b6a50376bd8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_dd618753-0a54-4386-b684-12206b98672e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_17c3f530-8ebd-40a8-b034-9b6a50376bd8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_eea81b25-3910-44a0-8ddb-d68e24381f64" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_dd618753-0a54-4386-b684-12206b98672e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_eea81b25-3910-44a0-8ddb-d68e24381f64" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_a4370f8b-1509-4f0d-b16b-bc14416f7485" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_dd618753-0a54-4386-b684-12206b98672e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_a4370f8b-1509-4f0d-b16b-bc14416f7485" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_311a84d8-ae1d-4913-a00d-a58235e476a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_dd618753-0a54-4386-b684-12206b98672e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_311a84d8-ae1d-4913-a00d-a58235e476a8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_1720da1b-8ca8-4c73-8039-412f86afcc7f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/EarningsperShareNarrativeDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#EarningsperShareNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/EarningsperShareNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionLineItems_8fa8bf7d-cff1-4643-a477-1735416cf42f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtConversionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionTable_62eb760d-0341-47ce-ad74-be69b2a7b67b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtConversionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtConversionLineItems_8fa8bf7d-cff1-4643-a477-1735416cf42f" xlink:to="loc_us-gaap_DebtConversionTable_62eb760d-0341-47ce-ad74-be69b2a7b67b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_014b26fe-77d7-4153-a309-7ccded159a62" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtConversionTable_62eb760d-0341-47ce-ad74-be69b2a7b67b" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_014b26fe-77d7-4153-a309-7ccded159a62" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_014b26fe-77d7-4153-a309-7ccded159a62_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_014b26fe-77d7-4153-a309-7ccded159a62" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_014b26fe-77d7-4153-a309-7ccded159a62_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_fbdf4047-731e-49e5-8d8d-6b9c1b94ac07" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_014b26fe-77d7-4153-a309-7ccded159a62" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_fbdf4047-731e-49e5-8d8d-6b9c1b94ac07" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_99f4556c-e10f-4f9f-8555-692daab594f3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_fbdf4047-731e-49e5-8d8d-6b9c1b94ac07" xlink:to="loc_us-gaap_ConvertibleDebtMember_99f4556c-e10f-4f9f-8555-692daab594f3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_f3b72c02-2727-4834-8499-f7cf103df119" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtConversionLineItems_8fa8bf7d-cff1-4643-a477-1735416cf42f" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_f3b72c02-2727-4834-8499-f7cf103df119" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_a191be52-f36c-42e9-885a-cdd989922f0b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtConversionLineItems_8fa8bf7d-cff1-4643-a477-1735416cf42f" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_a191be52-f36c-42e9-885a-cdd989922f0b" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/EarningsLossperShareScheduleofCommonStockEquivalentsExcludedintheCalculationofDilutedEarningsperShareDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#EarningsLossperShareScheduleofCommonStockEquivalentsExcludedintheCalculationofDilutedEarningsperShareDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/EarningsLossperShareScheduleofCommonStockEquivalentsExcludedintheCalculationofDilutedEarningsperShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_ce630d2d-712c-4812-bda5-e075b22c5f3e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_8341c6ac-5dae-444a-996e-ce284ef4c504" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_ce630d2d-712c-4812-bda5-e075b22c5f3e" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_8341c6ac-5dae-444a-996e-ce284ef4c504" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_f73d2e92-1a08-4659-bb7e-3b5d5865cba4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_8341c6ac-5dae-444a-996e-ce284ef4c504" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_f73d2e92-1a08-4659-bb7e-3b5d5865cba4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_f73d2e92-1a08-4659-bb7e-3b5d5865cba4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_f73d2e92-1a08-4659-bb7e-3b5d5865cba4" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_f73d2e92-1a08-4659-bb7e-3b5d5865cba4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_18c4f3ae-d12d-49e1-8e5c-9fc699aaad80" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_f73d2e92-1a08-4659-bb7e-3b5d5865cba4" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_18c4f3ae-d12d-49e1-8e5c-9fc699aaad80" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockCompensationPlanMember_64d0d159-5af9-4043-af35-5a332a008e7e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockCompensationPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_18c4f3ae-d12d-49e1-8e5c-9fc699aaad80" xlink:to="loc_us-gaap_StockCompensationPlanMember_64d0d159-5af9-4043-af35-5a332a008e7e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_b6772273-d534-4156-bdd6-b6d05bab3e25" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_18c4f3ae-d12d-49e1-8e5c-9fc699aaad80" xlink:to="loc_us-gaap_ConvertibleDebtMember_b6772273-d534-4156-bdd6-b6d05bab3e25" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_c972c874-204a-46b3-8c96-0be78f4a5900" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_ce630d2d-712c-4812-bda5-e075b22c5f3e" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_c972c874-204a-46b3-8c96-0be78f4a5900" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/IncomeTaxExpenseNarrativeDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#IncomeTaxExpenseNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/IncomeTaxExpenseNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsLineItems_89f30bab-207f-4204-bdb0-03cf64ac49ea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLossCarryforwardsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsTable_839d1706-bae2-4460-8fe6-a513835eca39" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLossCarryforwardsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_89f30bab-207f-4204-bdb0-03cf64ac49ea" xlink:to="loc_us-gaap_OperatingLossCarryforwardsTable_839d1706-bae2-4460-8fe6-a513835eca39" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityAxis_1ef9d041-afcf-444f-b730-e048290e710c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_839d1706-bae2-4460-8fe6-a513835eca39" xlink:to="loc_us-gaap_IncomeTaxAuthorityAxis_1ef9d041-afcf-444f-b730-e048290e710c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_1ef9d041-afcf-444f-b730-e048290e710c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_1ef9d041-afcf-444f-b730-e048290e710c" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_1ef9d041-afcf-444f-b730-e048290e710c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_8ef11dad-08be-4be7-9c20-85b1ced65c13" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_1ef9d041-afcf-444f-b730-e048290e710c" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_8ef11dad-08be-4be7-9c20-85b1ced65c13" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DomesticCountryMember_b9fab42d-6997-43d3-990f-d788d9fc00b3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DomesticCountryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_8ef11dad-08be-4be7-9c20-85b1ced65c13" xlink:to="loc_us-gaap_DomesticCountryMember_b9fab42d-6997-43d3-990f-d788d9fc00b3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StateAndLocalJurisdictionMember_41fbc6d9-8fc4-4b57-a631-2277e270440b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StateAndLocalJurisdictionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_8ef11dad-08be-4be7-9c20-85b1ced65c13" xlink:to="loc_us-gaap_StateAndLocalJurisdictionMember_41fbc6d9-8fc4-4b57-a631-2277e270440b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpense_1572f116-06bd-4d69-913b-25387ee9c981" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_89f30bab-207f-4204-bdb0-03cf64ac49ea" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpense_1572f116-06bd-4d69-913b-25387ee9c981" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwards_3181ae0b-9530-4eab-afda-05554865bf96" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLossCarryforwards"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_89f30bab-207f-4204-bdb0-03cf64ac49ea" xlink:to="loc_us-gaap_OperatingLossCarryforwards_3181ae0b-9530-4eab-afda-05554865bf96" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_NetOperatingLossCarryforwardUtilized_a4df5588-0380-40ff-81cb-938e25c01956" xlink:href="supn-20241231.xsd#supn_NetOperatingLossCarryforwardUtilized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_89f30bab-207f-4204-bdb0-03cf64ac49ea" xlink:to="loc_supn_NetOperatingLossCarryforwardUtilized_a4df5588-0380-40ff-81cb-938e25c01956" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefitsInterestOnIncomeTaxesAccrued_91a810fe-7dae-4ea2-85da-d5853c5e6c64" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_UnrecognizedTaxBenefitsInterestOnIncomeTaxesAccrued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_89f30bab-207f-4204-bdb0-03cf64ac49ea" xlink:to="loc_us-gaap_UnrecognizedTaxBenefitsInterestOnIncomeTaxesAccrued_91a810fe-7dae-4ea2-85da-d5853c5e6c64" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/LeasesNarrativeDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#LeasesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/LeasesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_1f3bb5c8-c6fd-4e1b-b885-b8dac8dbffb1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_bb09fadb-892b-4cdf-85a3-50b44380f6e7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_1f3bb5c8-c6fd-4e1b-b885-b8dac8dbffb1" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_bb09fadb-892b-4cdf-85a3-50b44380f6e7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_5d1efcd1-6468-4e85-89eb-4c7211a9b2cf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_bb09fadb-892b-4cdf-85a3-50b44380f6e7" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_5d1efcd1-6468-4e85-89eb-4c7211a9b2cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_5d1efcd1-6468-4e85-89eb-4c7211a9b2cf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_5d1efcd1-6468-4e85-89eb-4c7211a9b2cf" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_5d1efcd1-6468-4e85-89eb-4c7211a9b2cf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9db01848-3ba4-41cd-8b21-ebb324ccdaa7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_5d1efcd1-6468-4e85-89eb-4c7211a9b2cf" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9db01848-3ba4-41cd-8b21-ebb324ccdaa7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MerzAgreementMember_9f1d945e-c2a5-42f1-9f93-1601588deddd" xlink:href="supn-20241231.xsd#supn_MerzAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9db01848-3ba4-41cd-8b21-ebb324ccdaa7" xlink:to="loc_supn_MerzAgreementMember_9f1d945e-c2a5-42f1-9f93-1601588deddd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_2b6b3a9b-78ce-43d9-9df7-5db428136334" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_1f3bb5c8-c6fd-4e1b-b885-b8dac8dbffb1" xlink:to="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_2b6b3a9b-78ce-43d9-9df7-5db428136334" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_LesseeOperatingLeaseNumberOfRenewalOptions_f165a303-e2b4-40b1-91f8-fda9af93095a" xlink:href="supn-20241231.xsd#supn_LesseeOperatingLeaseNumberOfRenewalOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_1f3bb5c8-c6fd-4e1b-b885-b8dac8dbffb1" xlink:to="loc_supn_LesseeOperatingLeaseNumberOfRenewalOptions_f165a303-e2b4-40b1-91f8-fda9af93095a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_PurchaseCommitmentAnnualMinimumAmountCommitted_dfb1f0cb-a1ff-42c9-b643-ec32e9e4ca49" xlink:href="supn-20241231.xsd#supn_PurchaseCommitmentAnnualMinimumAmountCommitted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_1f3bb5c8-c6fd-4e1b-b885-b8dac8dbffb1" xlink:to="loc_supn_PurchaseCommitmentAnnualMinimumAmountCommitted_dfb1f0cb-a1ff-42c9-b643-ec32e9e4ca49" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/SegmentReportingDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#SegmentReportingDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/SegmentReportingDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingAssetReconcilingItemLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReconciliationOfAssetsFromSegmentToConsolidatedTable_19b6b7b8-c213-4b36-9e1a-973f25cf1433" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReconciliationOfAssetsFromSegmentToConsolidatedTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_ReconciliationOfAssetsFromSegmentToConsolidatedTable_19b6b7b8-c213-4b36-9e1a-973f25cf1433" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_9bfc207f-95f9-4db5-90c8-6c6f2e9a14cc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ReconciliationOfAssetsFromSegmentToConsolidatedTable_19b6b7b8-c213-4b36-9e1a-973f25cf1433" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_9bfc207f-95f9-4db5-90c8-6c6f2e9a14cc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_9bfc207f-95f9-4db5-90c8-6c6f2e9a14cc_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_9bfc207f-95f9-4db5-90c8-6c6f2e9a14cc" xlink:to="loc_us-gaap_SegmentDomain_9bfc207f-95f9-4db5-90c8-6c6f2e9a14cc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_2ee76f18-f277-44ba-b28f-8aadae600d11" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_9bfc207f-95f9-4db5-90c8-6c6f2e9a14cc" xlink:to="loc_us-gaap_SegmentDomain_2ee76f18-f277-44ba-b28f-8aadae600d11" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_ReportableSegmentMember_da111426-530c-45dc-acbe-a5fd53d33d6f" xlink:href="supn-20241231.xsd#supn_ReportableSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_2ee76f18-f277-44ba-b28f-8aadae600d11" xlink:to="loc_supn_ReportableSegmentMember_da111426-530c-45dc-acbe-a5fd53d33d6f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_0023c83a-7cb4-4d9a-9e42-ebf6cd9ca05b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ReconciliationOfAssetsFromSegmentToConsolidatedTable_19b6b7b8-c213-4b36-9e1a-973f25cf1433" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_0023c83a-7cb4-4d9a-9e42-ebf6cd9ca05b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0023c83a-7cb4-4d9a-9e42-ebf6cd9ca05b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_0023c83a-7cb4-4d9a-9e42-ebf6cd9ca05b" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0023c83a-7cb4-4d9a-9e42-ebf6cd9ca05b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_a100f375-9134-4b9a-9ef9-b688a77fc26b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_0023c83a-7cb4-4d9a-9e42-ebf6cd9ca05b" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_a100f375-9134-4b9a-9ef9-b688a77fc26b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_ONAPGOMember_f8731091-c6fd-431d-9cfa-d85a93715915" xlink:href="supn-20241231.xsd#supn_ONAPGOMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_a100f375-9134-4b9a-9ef9-b688a77fc26b" xlink:to="loc_supn_ONAPGOMember_f8731091-c6fd-431d-9cfa-d85a93715915" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_SPN820Member_7147e565-cdad-4106-a6fe-d4039e1669c4" xlink:href="supn-20241231.xsd#supn_SPN820Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_a100f375-9134-4b9a-9ef9-b688a77fc26b" xlink:to="loc_supn_SPN820Member_7147e565-cdad-4106-a6fe-d4039e1669c4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_SPN817Member_d6b1bcda-10e8-49c1-ac17-1c6d5d2f69c9" xlink:href="supn-20241231.xsd#supn_SPN817Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_a100f375-9134-4b9a-9ef9-b688a77fc26b" xlink:to="loc_supn_SPN817Member_d6b1bcda-10e8-49c1-ac17-1c6d5d2f69c9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_QelbreeMember_f73ba92f-a456-4af2-b2ce-eaa6100cf4ca" xlink:href="supn-20241231.xsd#supn_QelbreeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_a100f375-9134-4b9a-9ef9-b688a77fc26b" xlink:to="loc_supn_QelbreeMember_f73ba92f-a456-4af2-b2ce-eaa6100cf4ca" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_EarlyStageProgramAndOtherMember_170d74e1-e616-492c-abc4-f985f613fdf2" xlink:href="supn-20241231.xsd#supn_EarlyStageProgramAndOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_a100f375-9134-4b9a-9ef9-b688a77fc26b" xlink:to="loc_supn_EarlyStageProgramAndOtherMember_170d74e1-e616-492c-abc4-f985f613fdf2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_80288334-81b3-42c7-9e34-003a1382e1ee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_80288334-81b3-42c7-9e34-003a1382e1ee" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_c04109e1-af0a-41b8-a5f1-09fd4527906c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_c04109e1-af0a-41b8-a5f1-09fd4527906c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingExpense_5efc842b-78bd-4e64-90b9-00a721eeb1bf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_SellingExpense_5efc842b-78bd-4e64-90b9-00a721eeb1bf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketingExpense_5894b422-1776-4706-8fdc-c023183992f0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MarketingExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_MarketingExpense_5894b422-1776-4706-8fdc-c023183992f0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_d76c3a81-3908-4f68-ba1b-0b65277297b7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_d76c3a81-3908-4f68-ba1b-0b65277297b7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_ExternalResearchAndDevelopmentExpense_c2829bd5-aec2-4710-897e-2aa1923cb542" xlink:href="supn-20241231.xsd#supn_ExternalResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_supn_ExternalResearchAndDevelopmentExpense_c2829bd5-aec2-4710-897e-2aa1923cb542" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_InternalResearchAndDevelopmentExpense_404b4ff4-ec30-4771-aeff-00bf2bb5aca0" xlink:href="supn-20241231.xsd#supn_InternalResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_supn_InternalResearchAndDevelopmentExpense_404b4ff4-ec30-4771-aeff-00bf2bb5aca0" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_2b96cc44-7992-4176-9496-e99eed03a7fc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_2b96cc44-7992-4176-9496-e99eed03a7fc" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_52dfb23c-56dc-4541-833b-3d369be8456d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_52dfb23c-56dc-4541-833b-3d369be8456d" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_994480cf-9b0c-4015-b0a6-72b9ff8a8a6c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingAssetReconcilingItemLineItems_bb59a4cb-d8e2-47bf-84fb-461ad95337e5" xlink:to="loc_us-gaap_NetIncomeLoss_994480cf-9b0c-4015-b0a6-72b9ff8a8a6c" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/CompositionofOtherBalanceSheetItemsPropertyandEquipmentDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#CompositionofOtherBalanceSheetItemsPropertyandEquipmentDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/CompositionofOtherBalanceSheetItemsPropertyandEquipmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_3e349de0-9ac1-494b-9b92-1b058155c4dd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_3d96ec07-d9b4-4cb3-a7c5-836c043e1056" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_3e349de0-9ac1-494b-9b92-1b058155c4dd" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_3d96ec07-d9b4-4cb3-a7c5-836c043e1056" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_db599a8a-d34f-42e8-b069-a65359078f3d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_3d96ec07-d9b4-4cb3-a7c5-836c043e1056" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_db599a8a-d34f-42e8-b069-a65359078f3d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_db599a8a-d34f-42e8-b069-a65359078f3d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_db599a8a-d34f-42e8-b069-a65359078f3d" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_db599a8a-d34f-42e8-b069-a65359078f3d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_05414fb1-110d-46d2-9c2f-68c0f67922ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_db599a8a-d34f-42e8-b069-a65359078f3d" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_05414fb1-110d-46d2-9c2f-68c0f67922ec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_LabEquipmentAndFurnitureMember_50b402d2-592e-460a-a138-a24ab6e6a131" xlink:href="supn-20241231.xsd#supn_LabEquipmentAndFurnitureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_05414fb1-110d-46d2-9c2f-68c0f67922ec" xlink:to="loc_supn_LabEquipmentAndFurnitureMember_50b402d2-592e-460a-a138-a24ab6e6a131" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_b02bad5e-d8c9-4c0c-ae14-389649259eac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_05414fb1-110d-46d2-9c2f-68c0f67922ec" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_b02bad5e-d8c9-4c0c-ae14-389649259eac" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_88df62d7-7f15-4d9a-89b5-1765e32b4739" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SoftwareAndSoftwareDevelopmentCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_05414fb1-110d-46d2-9c2f-68c0f67922ec" xlink:to="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_88df62d7-7f15-4d9a-89b5-1765e32b4739" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_95aac083-a85d-4426-9c3c-13f840f0fbc3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_05414fb1-110d-46d2-9c2f-68c0f67922ec" xlink:to="loc_us-gaap_ComputerEquipmentMember_95aac083-a85d-4426-9c3c-13f840f0fbc3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_03ee4292-5f96-47c8-acb2-dec1203ffc72" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_3e349de0-9ac1-494b-9b92-1b058155c4dd" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_03ee4292-5f96-47c8-acb2-dec1203ffc72" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_9dad1464-6eda-47e1-b0f1-e40f8a3456d8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_3e349de0-9ac1-494b-9b92-1b058155c4dd" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_9dad1464-6eda-47e1-b0f1-e40f8a3456d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_47580d9f-48bd-40b3-b173-684380b967eb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_3e349de0-9ac1-494b-9b92-1b058155c4dd" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_47580d9f-48bd-40b3-b173-684380b967eb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationAndAmortization_0198cfad-c006-4ad5-ab9c-9a2bb5b0aaab" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DepreciationAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_3e349de0-9ac1-494b-9b92-1b058155c4dd" xlink:to="loc_us-gaap_DepreciationAndAmortization_0198cfad-c006-4ad5-ab9c-9a2bb5b0aaab" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/CommitmentsandContingenciesDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#CommitmentsandContingenciesDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/CommitmentsandContingenciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermPurchaseCommitmentLineItems_8e7e9cfb-a5ab-4f18-9aa3-2f191edb1e55" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermPurchaseCommitmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermPurchaseCommitmentTable_35bebd19-0495-41b3-b46f-1f35d27928d8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermPurchaseCommitmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LongTermPurchaseCommitmentLineItems_8e7e9cfb-a5ab-4f18-9aa3-2f191edb1e55" xlink:to="loc_us-gaap_LongTermPurchaseCommitmentTable_35bebd19-0495-41b3-b46f-1f35d27928d8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_434b1fed-7b9c-41c5-a700-d0e35c2f3456" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LongTermPurchaseCommitmentTable_35bebd19-0495-41b3-b46f-1f35d27928d8" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_434b1fed-7b9c-41c5-a700-d0e35c2f3456" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_434b1fed-7b9c-41c5-a700-d0e35c2f3456_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_434b1fed-7b9c-41c5-a700-d0e35c2f3456" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_434b1fed-7b9c-41c5-a700-d0e35c2f3456_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_2801a31c-d15c-41f8-90d6-737c5b607ecd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_434b1fed-7b9c-41c5-a700-d0e35c2f3456" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_2801a31c-d15c-41f8-90d6-737c5b607ecd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_ccb1cc34-8b2e-4176-8086-db494a9d06f5" xlink:href="supn-20241231.xsd#supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_2801a31c-d15c-41f8-90d6-737c5b607ecd" xlink:to="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_ccb1cc34-8b2e-4176-8086-db494a9d06f5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseAxis_53d6d058-8e07-4691-b000-4bd018b034ea" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_LitigationCaseAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LongTermPurchaseCommitmentTable_35bebd19-0495-41b3-b46f-1f35d27928d8" xlink:to="loc_srt_LitigationCaseAxis_53d6d058-8e07-4691-b000-4bd018b034ea" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseTypeDomain_53d6d058-8e07-4691-b000-4bd018b034ea_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_LitigationCaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_LitigationCaseAxis_53d6d058-8e07-4691-b000-4bd018b034ea" xlink:to="loc_srt_LitigationCaseTypeDomain_53d6d058-8e07-4691-b000-4bd018b034ea_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseTypeDomain_347d1040-fa35-43b3-94a1-70f2d14c7f85" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_LitigationCaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_LitigationCaseAxis_53d6d058-8e07-4691-b000-4bd018b034ea" xlink:to="loc_srt_LitigationCaseTypeDomain_347d1040-fa35-43b3-94a1-70f2d14c7f85" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_NAMENDAXRNamzaricQuiTamLitigationMember_d15a54af-d290-4027-9865-63746b4aea07" xlink:href="supn-20241231.xsd#supn_NAMENDAXRNamzaricQuiTamLitigationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_LitigationCaseTypeDomain_347d1040-fa35-43b3-94a1-70f2d14c7f85" xlink:to="loc_supn_NAMENDAXRNamzaricQuiTamLitigationMember_d15a54af-d290-4027-9865-63746b4aea07" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_PurchaseCommitmentAnnualMinimumAmountCommitted_03da9a8b-87eb-4830-8292-a49cc4a59c16" xlink:href="supn-20241231.xsd#supn_PurchaseCommitmentAnnualMinimumAmountCommitted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermPurchaseCommitmentLineItems_8e7e9cfb-a5ab-4f18-9aa3-2f191edb1e55" xlink:to="loc_supn_PurchaseCommitmentAnnualMinimumAmountCommitted_03da9a8b-87eb-4830-8292-a49cc4a59c16" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationSettlementAmountAwardedToOtherParty_bd69ab00-31bc-451c-9586-c945956351b3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LitigationSettlementAmountAwardedToOtherParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermPurchaseCommitmentLineItems_8e7e9cfb-a5ab-4f18-9aa3-2f191edb1e55" xlink:to="loc_us-gaap_LitigationSettlementAmountAwardedToOtherParty_bd69ab00-31bc-451c-9586-c945956351b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingencyDamagesSoughtValue_75337391-fb73-4a92-a471-75aca9555669" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LossContingencyDamagesSoughtValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermPurchaseCommitmentLineItems_8e7e9cfb-a5ab-4f18-9aa3-2f191edb1e55" xlink:to="loc_us-gaap_LossContingencyDamagesSoughtValue_75337391-fb73-4a92-a471-75aca9555669" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.supernus.com/role/SubsequentEventsDetails" xlink:type="simple" xlink:href="supn-20241231.xsd#SubsequentEventsDetails"/>
  <link:definitionLink xlink:role="http://www.supernus.com/role/SubsequentEventsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_88c88374-fc5a-4645-835c-cd93b11d5595" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_83943a5b-b4e3-48c6-96e5-f78c41b22e05" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_88c88374-fc5a-4645-835c-cd93b11d5595" xlink:to="loc_us-gaap_SubsequentEventTable_83943a5b-b4e3-48c6-96e5-f78c41b22e05" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_a3fd7b6b-5839-40e3-b3a0-069a386b8844" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_83943a5b-b4e3-48c6-96e5-f78c41b22e05" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_a3fd7b6b-5839-40e3-b3a0-069a386b8844" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_a3fd7b6b-5839-40e3-b3a0-069a386b8844_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_a3fd7b6b-5839-40e3-b3a0-069a386b8844" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_a3fd7b6b-5839-40e3-b3a0-069a386b8844_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_a8c92e7f-59c9-4f6b-b7e1-6a22e7e4e76a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_a3fd7b6b-5839-40e3-b3a0-069a386b8844" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_a8c92e7f-59c9-4f6b-b7e1-6a22e7e4e76a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_a59c32dd-bdbd-4b63-897e-ae5f86ccba60" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_a8c92e7f-59c9-4f6b-b7e1-6a22e7e4e76a" xlink:to="loc_us-gaap_SubsequentEventMember_a59c32dd-bdbd-4b63-897e-ae5f86ccba60" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_3832f314-8424-4d14-bed4-684409e476b0" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_83943a5b-b4e3-48c6-96e5-f78c41b22e05" xlink:to="loc_srt_StatementScenarioAxis_3832f314-8424-4d14-bed4-684409e476b0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_3832f314-8424-4d14-bed4-684409e476b0_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_3832f314-8424-4d14-bed4-684409e476b0" xlink:to="loc_srt_ScenarioUnspecifiedDomain_3832f314-8424-4d14-bed4-684409e476b0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_080ed889-40cf-4e56-814a-5dcb79cea4bd" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_3832f314-8424-4d14-bed4-684409e476b0" xlink:to="loc_srt_ScenarioUnspecifiedDomain_080ed889-40cf-4e56-814a-5dcb79cea4bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_9c9b3912-78ed-4b5d-aca8-b68ebe97a220" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ScenarioForecastMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_080ed889-40cf-4e56-814a-5dcb79cea4bd" xlink:to="loc_srt_ScenarioForecastMember_9c9b3912-78ed-4b5d-aca8-b68ebe97a220" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_32eec442-1e0e-49af-a1b1-13ff09dd4d19" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_83943a5b-b4e3-48c6-96e5-f78c41b22e05" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_32eec442-1e0e-49af-a1b1-13ff09dd4d19" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_32eec442-1e0e-49af-a1b1-13ff09dd4d19_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_32eec442-1e0e-49af-a1b1-13ff09dd4d19" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_32eec442-1e0e-49af-a1b1-13ff09dd4d19_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_003c6756-e208-4973-a111-db4c890f1036" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_32eec442-1e0e-49af-a1b1-13ff09dd4d19" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_003c6756-e208-4973-a111-db4c890f1036" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_5fa5f579-9f93-43fe-b9bc-4dfe5b1e9de9" xlink:href="supn-20241231.xsd#supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_003c6756-e208-4973-a111-db4c890f1036" xlink:to="loc_supn_MDDUSEnterprisesLLCFormerlyUSWMEnterprisesMember_5fa5f579-9f93-43fe-b9bc-4dfe5b1e9de9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities_b8f61fec-7981-44c2-88eb-5e0522a5fcef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_88c88374-fc5a-4645-835c-cd93b11d5595" xlink:to="loc_us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities_b8f61fec-7981-44c2-88eb-5e0522a5fcef" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-roles-2024.xsd#eedm"/>
  <link:definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementAbstract" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:type="arc" order="691"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract" xlink:to="loc_us-gaap_OtherAssetsNoncurrent" xlink:type="arc" order="101"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#IndividualsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllIndividualsMember" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_AllIndividualsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_supn_JackKhattarMember_740d8a64-d8eb-4707-aad0-9ecf01cb076b" xlink:href="supn-20241231.xsd#supn_JackKhattarMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_supn_JackKhattarMember_740d8a64-d8eb-4707-aad0-9ecf01cb076b" xlink:type="arc" order="2"/>
  </link:definitionLink>
</link:linkbase>
