Purpose: The convergence of innovative biotechnologies is propelling the field of gene therapy with consequential implications for treating and curing genetic and infectious diseases globally. Although dozens of gene therapies for a broad range of disease areas are expected to receive regulatory approval worldwide over the next decade, patients are unlikely to receive equitable access to these medical breakthroughs. In particular, the sophisticated infrastructure required to deliver gene therapies pose critical challenges for low and middle-income countries (LMICs) seeking to integrate gene therapies into resource-constrained health systems. Without critical foresight and targeted investments across LMICs, gene therapies will perpetuate global health inequity. Materials and methods: Using gene therapies for sickle cell disease and human immunodeficiency virus (HIV) in sub-Saharan Africa as use cases, this project examined the necessary infrastructure required for effectively and sustainably delivering gene therapies in low-resource settings. Data was obtained through a series of interviews with expert stakeholders from sub-Saharan Africa, Europe, and the US. Interviewees represented multiple sectors including hospitals and community clinics, gene therapy companies, manufacturing, patient advocacy and community engagement, technical training, and global health priority setting. Interviews were supplemented with an extensive literature review. Results: An analysis of stakeholder interviews revealed the need for core infrastructure across seven thematic areas: research; engagement and education; facilities and manufacturing; information systems, workforce, regulation; and finance. Although assessed individually, these domains are interdependent, highlighting the need to invest and co-develop across all areas simultaneously and synergistically. Conclusion: Building the requisite infrastructure for delivering gene therapies is a multi-decade endeavour. This long horizon should not discourage immediate action; rather, it should be acknowledged and appreciated as an opportunity for strategic preparation assuring future success. By establishing and maintaining infrastructure across several thematic areas, countries can accelerate the development and delivery of gene therapies. Throughout this process, key steps should be taken to improve outcomes: Engage communities early and often: The process of providing gene therapies must be patient-centred. Involving communities in the design and implementation process will lead to effective therapies that are acceptable and accessible. Leverage existing infrastructure: Maximizing the impact of limited resources and removing redundancy requires integrated services, multi-use facilities, and increased coordination. Collaborate internationally: While countries in SSA build research capacity, promote private sector innovation and commercialization, and update regulatory frameworks, international collaboration will facilitate the exchange of scientific equipment, knowledge and training, and policy. Improve and adapt iteratively: The success of gene therapy hinges on iterative cycles of feedback between research and clinical deployment. Infrastructure should support the ability of scientific and societal findings to inform healthcare practices and regulations. While this study focuses on gene therapy delivery and its requisite infrastructure, considerations of health systems strengthening should remain at the forefront. The delivery of gene therapies should expand to align with health priorities set by countries (e.g., attention to non-communicable diseases). A narrow focus on gene therapies can create vertical systems of planning, management, and monitoring and evaluation that are not suited for other health areas and do not maximize the use of limited resources. The authors do not declare any conflict of interest