Although it has become commonplace to talk about the rural-urban divide, the reality is that the destinies of rural and urban people and places are intertwined. Many of the most difficult challenges we face, such as public health, climate change, food security, migration, energy, water, land use, and transportation, do not recognize boundaries. They demand cross-jurisdiction, cross-sectoral, cross-disciplinary responses. The Regional Solutions for Rural and Urban Challenges project explores how regional collaboration can help to improve social and economic opportunity and health for all people and places. Deborah Markley from LOCUS Impact Investing and Brian Dabson from the School of Government, University of North Carolina-Chapel Hill will describe the findings of this project and discuss their implications for philanthropy and philanthropy-serving organizations.