ABSTRACT The “Deep South,” including Alabama, Mississippi, and Louisiana, has the highest rates of obesity, diabetes and hypertension in the nation. As a result, life expectancy in the Deep South is substantially lower than other regions. The mission of the Deep South Center to Reduce Disparities in Chronic Diseases is to develop a regional research center focused on the prevention, treatment and management of cardiometabolic diseases among populations who suffer disproportionately from these conditions in Alabama, Mississippi, and Louisiana. The Center is unified thematically through the application of the precision public health approach across the care continuum to reduce the burden of cardiometabolic disease, as improving health outcomes will require precision public health, i.e., “providing the right intervention to the right population at the right time.” This approach acknowledges the importance of context, individual beliefs and preferences as well as the need for multi-level and multi-domain interventions. The Center brings together an interdisciplinary team of investigators from 4 institutions in 3 contiguous states (the University of Alabama at Birmingham, Tuskegee University, Louisiana’s Pennington Biomedical Research Center, and the University of Mississippi Medical Center) as well as regional non-academic partners to extend cardiometabolic research into real-world community and clinical settings. The Center will drive academic and nonacademic partners toward a new level of intellectual synergy, collaboration, and sustainable efforts to disseminate effective interventions that improve health outcomes in the region. To achieve the long-term goal of improving population health, the Center will provide and coordinate resources not currently available through the following: 1) an Investigator Development Core, to expand the region’s research workforce through enrichment activities and a robust pilot program; 2) a Community Engagement Core, to promote effective bi-directional collaborations between researchers and non-academic partners; and 3) the Administrative Core, to provide leadership and support for all Center initiatives. The Center also includes three interrelated research projects evaluating multi-level and multi-domain interventions that are informed by, and conducted with, academic and community partners in the region to improve cardiometabolic health outcomes among populations with persistent chronic disease burden. Given the significant burden of cardiometabolic diseases evident in the Deep South, the strong research base present at the partnering institutions, and the potential to expand and focus these energies on health outcomes research, the Deep South Center to Reduce Disparities in Chronic Diseases is ideally situated to inform research, clinical care, and policy to improve cardiometabolic health outcomes in a region of tremendous need.