In an effort to help build the evidence base around the social determinants of health (SDOH), the Assistant Secretary for Planning and Evaluation (ASPE) engaged RAND in a project to evaluate the current evidence from programs and policies targeting SDOH and identify the SDOH research questions, data sources, and data gaps that might be used to develop an SDOH research agenda. RAND used a multimethods approach that included an environmental scan of the published and gray literature of SDOH interventions; key informant interviews with subject matter experts; and a convening of U.S. Department of Health and Human Services (HHS) agencies and operating divisions to review the results of the environmental scan and offer insights on the findings. While this project identified a range of health benefits related to SDOH interventions, gaps remain in our understanding of what works to address certain types of social determinants, the specific intervention components that improve health, and which interventions might achieve sustained and lasting improvements in population health. To grow the evidence base, investments are needed from a broad range of funders including philanthropy and organizations within the health care industry. Further, an HHS-driven SDOH research agenda can help support approaches to close these gaps.