Living in poverty and living in areas of concentrated poverty pose multiple risks for child development and for overall health and wellbeing. Poverty is a major risk factor for several mental, emotional, and behavioral disorders, as well as for other developmental challenges and physical health problems. In this paper, the Promise Neighborhoods Research Consortium describes a science-based framework for the promotion of child health and development within distressed high-poverty neighborhoods. We lay out a model of child and adolescent developmental outcomes and integrate knowledge of potent and malleable influences to define a comprehensive intervention framework to bring about a significant increase in the proportion of young people in high-poverty neighborhoods who will develop successfully. Based on a synthesis of research from diverse fields, we designed the Creating Nurturing Environments framework to guide community-wide efforts to improve child outcomes and reduce health and educational inequalities.