To further build knowledge of effective services for families in which adult substance use dependence may place children at risk for maltreatment, the Children’s Bureau contracted with Mathematica to design and conduct a national cross-site evaluation. To guide the evaluation design, Mathematica developed a conceptual framework using implementation science principles to show how the RPG projects will implement evidence-based programs and practices (EBPs), and how implementation is connected to outcomes for children adults, and families, and the effectiveness of the overall RPG program. Based on the framework, the evaluation includes (1) a study of the characteristics and functioning of the regional partnerships and the quality of their collaboration, using social network analysis; (2) an implementation study examining the use of over 50 EBPs, with an in-depth examination of ten high-interest models; (3) an outcomes study of changes that occur in children, adults and families in five domains (child well-being, permanency, and safety; family functioning and stability; and adult recovery from substance use dependence); and (4) an impact study of the effectiveness of RPG programs implemented by a subset of grantees conducting comparison group evaluations.