International interest is growing concerning using strength-based models of adolescent development to understand how mutually influential relations between individuals and their key settings may be a basis for positive, healthy development. Bidirectional relations models are linked to relational developmental systems (RDS) metatheory, with a focus on the positive youth development (PYD) model, the most used ininternational PYD-related research and programs. A three-nation, counterfactual, comparative, longitudinal study is described to understand if Compassion International programs enhance thriving of the world’s poorest youth. RDS metatheory ideas point to the need for longitudinal studies using measures reflecting reliability, validity, and invariance across people, time, and place. This research should be framed by the “specificity principle” to identify individual and setting combinations that capitalize on the strengths of youth and place young people on a thriving trajectory.