PROJECT SUMMARY/ABSTRACT To support the Centers for Disease Control and Prevention (CDC) and states and communities in identifying programs, policies, or practices (PPP) that can reduce the ever-widening gaps in chronic disease incidence and mortality in the United States, we will develop a model to explore the impacts of social determinants of health (SDOH) factors on chronic disease incidence, mortality, and disparities over the next 5 to 30 years. We will use a systems science approach to create a mathematical simulation model that integrates risk and SDOH factors for the incidence of heart disease, stroke, diabetes, CKD, cancer, and Alzheimer’s disease, accounting for the interconnectedness and feedback loops between SDOH and chronic disease. The model will incorporate evidence-based strategies for addressing SDOH factors in each of the five priority areas for CDC’s National Center for Chronic Disease Prevention and Health Promotion: the built environment, community-clinical linkages, food and nutrition security, tobacco-free policy, and social connectedness. By generating synthetic populations to represent the SDOH-related characteristics (e.g., race/ethnicity, sex, age, income, education, and urban vs. rural status) and chronic disease risk factors of the selected county or state population, the model will produce valid results for each county and state in the United States. The model will also be calibrated to national surveillance data. We will develop a multi-user, web-based, public-use version of the model to operate on CDC’s web platforms. CDC and public health partner groups can run scenarios using the model to explore which combinations of PPPs would have the greatest impact on reducing chronic disease disparities and outcomes and how PPPs compare in terms of costs and cost- effectiveness. Results from the model will inform future public health practices related to SDOH. Moreover, the publicly available model will allow community members and public health interest groups to create scenarios and explore the impacts of various PPPs on health outcomes and disparities, thus encouraging the use of community-based participatory processes and decision-making around solutions to address SDOH and reduce disparities in chronic disease risk factors, incidence, and mortality.