In the summer of 2015, the East Tennessee State University (ETSU) College of Public Health and regional health systems serving 29 counties in Northeast Tennessee and Southwest Virginia began the process of identifying a set of high-impact health programs for inclusion in a ten-year regional plan to break the cycle of inter-generational poor health outcomes in this region. It was decided that selection of effective health improvement programming must be driven by a comprehensive and deliberate effort to garner input from communities and stakeholders across the region. More than 170 professionals representing 96 health-related agencies volunteered to form steering committees around four topic areas: healthy children and families, population health, mental health and addictions, and research and academics. Each committee was tasked with; 1) providing information to the health systems on regional health priorities, 2) identifying effective approaches to addressing them, and 3) pinpointing opportunities for cross-sector collaboration. Community input was secured by holding meetings in ten area counties using the World Café model; a format chosen to encourage and facilitate discussion between participants around their local community's health concerns. In addition to priority setting for the 10-year plan, cross-sector commitment and community buy-in was established during this process that will serve as the basis for organizational planning of a proposed accountable care community (ACC). Challenges and opportunities uncovered during our efforts to improve regional health outcomes through a collaborative approach may benefit other communities working on similar projects.