The Southeastern United States exhibits some of the highest prevalence levels associated with the leading causes of mortality. Among these, diabetes remains a concern in Mississippi, particularly within the Mississippi Delta region. This area shares borders with counties in Arkansas and Louisiana where diabetes prevalence levels range between 20% and 22%. These figures represent some of the highest levels in the nation. Furthermore, the prevalence of coronary heart disease in these areas is significantly higher than the national average with notable elevations in Arkansas, northwest Louisiana, and western Mississippi counties. Obesity prevalence in this region is also alarmingly high. This chapter explores these health issues and provides a spatial examination of the study area. It concludes by highlighting key initiatives undertaken by each state aimed at reducing these prevalence levels and improving overall health outcomes.