Rates of obesity and related non-communicable diseases are on the rise in sub-Saharan Africa, associated with sub-optimal diet and physical inactivity. Implementing evidence-based interventions targeting determinants of unhealthy eating and physical inactivity in children and adolescents’ immediate environments is critical to the fight against obesity and related non-communicable diseases. Setting priorities requires a wide range of stakeholders, methods, and context-specific data. This paper reports on a novel participatory study design to identify and address contextual drivers of unhealthy eating and physical inactivity of children and adolescents in school and in their home neighborhood food and built environments. We developed a three-phase mixed-method study in Cameroon (Yaoundé) and South Africa (Johannesburg and Cape Town) from 2020–2021. Phase one focused on identifying contextual drivers of unhealthy eating and physical inactivity in children and adolescents in each setting using secondary analysis of qualitative data. Phase two matched identified drivers to evidence-based interventions. In phase three, we worked with stakeholders using the Delphi technique to prioritize interventions based on perceived importance and feasibility. This study design provides a rigorous method to identify and prioritize interventions that are tailored to local contexts, incorporating expertise of diverse local stakeholders.