How can programs advance the well-being and self-sufficiency of at-risk youth? This brief summarizes a research-based framework for efforts to help at-risk youth enter a career workforce trajectory and prepare to become well-functioning, self-sufficient adults. The framework that is particularly relevant for youth who are or could be served by ACF programs—especially homeless youth, youth in the foster care system, and teen parents—but may also apply to other programs. The framework proposes using evidence-informed interventions to address two primary areas: youths’ resilience and human capital development. It suggests finding tailored solutions grounded in a trusting relationship between youth and program staff to help move youth toward both healthy functioning and economic self-sufficiency as they transition to adulthood. This brief was developed as part of the Youth Demonstration Development project, conducted by Mathematica Policy Research and Chapin Hall Center for Children.