ABSTRACT The burden of health disparities is most evident in the southeastern United States, where populations suffer the highest rates of cardiovascular disease, diabetes, obesity, hypertension, cancer, and asthma. These chronic conditions are a primary cause of poor health, reduced quality of life, and premature death, and account for more than 50% of health care expenditures. Despite substantial reduction of some chronic diseases and risk factors over the last few decades, the Southeast continues to have the highest number of potentially preventable deaths for each of the five leading causes of death. People living in the Southeast fare worse on many health indicators compared to other regions, in large part due to poor socioeconomic status, with more than 22% of Southeastern residents living in poverty. Effectively addressing pervasive chronic diseases will require interventions that consider the needs, priorities, and lived experiences of those impacted. Research teams with expertise in social, environmental, behavioral, and biological disciplines must collaborate to develop and test multicomponent strategies aimed at the multilevel determinants that drive chronic diseases. Via a new center - the Southeast Collaborative for Innovative Solutions to Chronic Diseases, we will bring together Vanderbilt University Medical Center, University of Miami, and Meharry Medical College to reduce risk factors for diabetes, cardiovascular disease, obesity, and related conditions among populations in the Southeast. We aim to: 1) Establish the human and technical infrastructure to foster highly collaborative, transdisciplinary research collaborations focused on using technology and data science to reduce chronic diseases among populations in the southeastern United States. 2) Facilitate a regional, cross-institutional pilot awards program focused on chronic diseases that nurtures and supports career development, advances use of data science, technology, and bioinformatics to address the complex drivers of chronic diseases. 3) Propel novel research leveraging technology, individual-level and community-level health data, and genomic and phenotypic data to prevent, treat, and manage diabetes, cardiovascular disease, obesity and related conditions. 4) Partner with communities in the Southeast to integrate their priorities into the Center’s infrastructure, and collaboratively develop, adapt, and test interventions to secure the earliest impact on eliminating chronic diseases.