Challenges exist in the study of social determinants of health (SDH) because of limited comparability of population-based U.S. data on SDH. This limitation is due to differences in disparity or equity measurements, as well as general data quality and availability. We reviewed the current SDH variables collected for HIV, viral hepatitis, sexually transmitted diseases, and tuberculosis at the Centers for Disease Control and Prevention through its population-based surveillance systems and assessed specific system attributes. Results were used to provide recommendations for a core set of SDH variables to collect that are both feasible and useful. We also conducted an environmental literature scan to determine the status of knowledge of SDH as underlying causes of disease and to inform the recommended core set of SDH variables.