Adolescents and sexual minority men (SMM) are high priority groups in the United Nations’ 2021 − 2016 goals for HIV prevention and viral load suppression. Interventions aimed at optimizing HIV prevention, testing and viral load suppression for adolescents must also attend to the intersectional realities influencing key sub-populations of SMM. Consequently, there is not a robust evidence-base to guide researchers and program partners on optimal approaches to implementing interventions with adolescent SMM. Using a multiple case study design, we integrated the Implementation Research Logic Model with components of the Consolidated Framework for Implementation Research and applied it as a framework for a comparative description of ten HIV related interventions implemented across five countries (Ghana, Kenya, Nigeria, Tanzania and United States). Using self-reported qualitative survey data of project principal investigators, we identified 17 of the most influential implementation determinants as well as a range of 17 strategies that were used in 90 instances to support intervention implementation. We highlight lessons learned in the implementation research process and provide recommendations for researchers considering future HIV implementation science studies with adolescent SMM.