Background <p>Despite significant progress in HIV prevention and treatment, uptake of evidence-based interventions among adolescents and young adults (AYA), particularly in low- and middle-income countries (LMICs), remains low. Implementation research can optimize strategies to enhance reach, uptake, and equitable access to these innovations. The Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource-Constrained Settings Implementation Science Network (PATC³H-IN) leverages implementation science to strengthen the delivery and sustainability of evidence-based HIV prevention and care for AYA across six countries in sub-Saharan Africa. This paper outlines PATC³H-IN’s goals, summarizes the implementation science (IS) data that will be collected, and highlights the advantages of research networks in advancing science.</p> Methods <p>The PATC³H-IN builds on the existing PATC³H consortium to advance IS research targeting AYA in LMICs. The PATC³H-IN comprises eight Clinical Research Centers (CRCs) located in Nigeria, Uganda, Malawi, South Africa, Zambia, and Tanzania. Representatives from the CRCs were asked to provide information on the IS components of their proposed studies, including details on study populations, IS frameworks, outcomes, and strategies, mechanisms of change, effectiveness outcomes, and documentation of intervention adaptations. The reports from the CRCs were compared to identify opportunities for advancing science across study sites.</p> Results <p>The PATC³H-IN studies will enroll AYA aged 12–24 years, with some emphasizing key subpopulations, namely AYA living with HIV, sexual and gender minorities, and adolescent girls and young women. All PATC³H-IN studies will be guided by one or more implementation science frameworks and theories, with the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework most frequently cited (<i>n</i> = 4/8). Across the CRCs, 54 unique implementation strategies will be used, with community engagement being the most common. Several studies will document intervention adaptations, and all studies will collect a set of common data elements to facilitate secondary data analyses across projects.</p> Conclusions <p>The PATC³H-IN represents a significant contribution to advancing HIV prevention and care research for AYA in resource-constrained settings. Findings from PATC³H-IN will extend our understanding of IS in sub-Saharan Africa, a region particularly burdened by HIV, and for AYA who are traditionally under-represented in IS research.</p> Clinical trial number <p>Not Applicable.</p>