Recent systematic reviews of adolescent and youth sexual and reproductive health (AYSRH) programming in low and middle -income countries have helped to assess the spectrum of AYSRH interventions and effectiveness. The most promising AYSRH interventions combine training and facility modifications to enable youth-friendly service provision with community engagement and demand generation. However, even the most promising interventions most efficaciously change attitudes, beliefs and intentions rather than behavior. As such, further research is needed to understand the “mechanisms of action” that lead to effective behavior change. As the global reproductive health community strives to improve health outcomes of the most vulnerable youth, putting the beneficiaries at the center of the intervention design process will facilitate a better understanding of the pathways to behavior change. A transdisciplinary approach integrating the fields of public health, adolescent developmental science, cultural anthropology, youth engagement, social marketing, and human-centered design offers meaningful insights into the mechanisms informing effective AYSRH interventions. Launched in 2016, Adolescents360 (A360)– a project aiming to increase contraceptive uptake among young women ages 15-19 in Ethiopia, Nigeria, and Tanzania – offers an exemplar of how an integrated, user-centered approach provides insights that enhance the precision – in both developmental timing and message targeting – of effective AYSRH interventions.