ABSTRACT The Innovative Network on the Science and Practice of Implementation, Research, and Engagement Center (INSPIRE) seeks to advance the science and practice of dissemination and implementation (D&I) science research in low-to-middle income countries by adapting, scaling up, and sustaining evidence-based HIV interventions for adolescents and young adults (AYA). The Center offers a unique opportunity to conduct this paradigm-shifting work as part of the Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected adolescents in resource-constrained settings implementation science network (PATC3H-IN). Using an Appreciative Inquiry lens that focuses on the strengths within a system that fuels change, our mission is to serve as a hub for optimizing synergistic D&I research that appreciates, coordinates, and magnifies insights on adaptation, scalability, and sustainability with communities of interest from across the network via our Capacity Supporting Core (CSC), Advanced Methods and Modeling Core (AAMC), and Community Engagement and Dissemination Core (CEDC). Communities of interest in the six PATC3H-IN countries (Nigeria, Malawi, Kenya, South Africa, Zambia, Tanzania) include researchers, implementers, community members, policymakers, and family members (especially guardians), friends, and adolescents and young adults (AYA). Our vision aligns with global goals to end the HIV epidemic among AYA. Our specific aims are: 1) Design and deliver cutting-edge implementation science training tailored to the needs of the HIV response to adolescents (Capacity Supporting Core); 2) Provide advanced methods and modeling expertise to combine diverse insights from the individual PATC3H-IN Clinical Research Centers (CRCs) together (Advanced Methods and Modeling Core); 3) Develop a shared strategy for community engagement and disseminating insights from PATC3H-IN to key communities of interest (Community Engagement and Dissemination Core); and 4) Evaluate INSPIRE progress and iteratively adapt, improve, and contribute to the network and science (Administration and Evaluation Unit). By creating a centralized mechanism to harness strength, listen, and convene across the networks, the INSPIRE Center will provide training, advanced methods, and engagement functions that will augment the findings of each CRC individual study across the HIV prevention and treatment care continuums, thus reducing inequities for AYA populations in LMIC settings and optimizing the translation of research findings into real-world impact.