Background and Objective <p>Over the last decade, payers in the USA have been exploring novel financing mechanisms for gene therapies (GTs). Our research objective was to assess the landscape of innovative contracts (ICs) between payers and manufacturers for GTs and identify barriers and opportunities for future contract development and implementation.</p> Methods <p>We used a multi-method approach including a targeted literature review and interviews. We developed a framework defining ‘innovative contracts’ as agreements using real-world outcomes that link to the total price paid for gene therapy, encompassing value-based pricing, outcome-based payments, and performance-based models between payers and manufacturers. We searched for published information about implementation of ICs for GTs in PubMed and government, industry, and research institutions from January 2014 to January 2025. We excluded any insights specific to ICs for non-GTs as well as those relevant to ex-US markets. We supplemented these findings with bibliographic searches. Semi-structured interviews with payers, manufacturers, and other diverse representatives from the GT financing ecosystem were conducted to validate and enrich the literature findings.</p> Results <p>The PubMed search yielded ten studies relevant to implementation of ICs. Gray literature included over 50 publications referencing active contracts, policy solutions, payer budget impact, and state Medicaid programs’ innovative GT contracting. Information on manufacturer and payer contracts was publicly available for 10 of 14 gene therapies (71%). Of 16 identified GT contracts, eight used upfront payments with milestone-based rebates, two used performance-based installment payments, one offered upfront payment with a rebate or payment over 5 years, and five do not have publicly available details on the type of financial arrangement. Interviews (<i>N</i> = 15) suggested that barriers to ICs include a lack of mutual trust between payers and manufacturers, lack of data conveying the return on investment for innovative contracts, lack of a sufficient incentive for stakeholders to engage in contracting, perceived regulatory limitations (e.g., implications of Medicaid Best Price), and patient portability challenges. Some interviewees believed that ICs should be the standard for GTs, while others stated that ICs should only be pursued when they are expected to have a significant impact on timely patient access in the early launch period when payers are considering limited or no coverage. Interviewees indicated that policy changes may encourage future contracting negotiation and implementation.</p> Conclusions <p>Widespread uptake of ICs will require a multi-stakeholder collaboration to overcome common barriers, as a one-size-fits-all approach is insufficient for diverse stakeholder needs. Establishing industry-wide contracting principles and practices may help bridge differences in opinions and build trust between contracting parties, allow stakeholders to share lessons from early adopters, and support efficient contracting processes that promote consistent and equitable patient access to GTs while ensuring healthcare system sustainability.</p>