OBJECTIVES: A polysocial risk score, which summarizes multiple health-related social needs (HRSNs) into a single likelihood of risk, could support more effective population health management. Nevertheless, a polysocial risk score faces uncertainties and challenges due to the HRSNs' differing etiologies and interventions, cooccurrence, and variation in information availability. STUDY DESIGN: A national expert panel provided guidance on the development and potential application of a polysocial risk score in a 3-round Delphi process. METHODS: Expert panel members from across the US included physicians (n = 8), social service professionals and staff (n = 9), and patients (n = 6). Round 1 obtained an initial sense of the importance of HRSNs for general health and well-being and total health care cost. Panelists also suggested additional HRSNs. Responses served as discussion points for round 2, during which 5 focus groups explored how HRSNs should be ranked, additional HRSNs to include, timing of measurements, management of nonresponse and missing data, and concerns about bias and equity. We analyzed the transcripts using a consensus coding approach. Panelists then completed a follow-up survey (round 3). RESULTS: Panelists identified 17 HRSNs relevant to health and well-being for inclusion in a polysocial risk score. Methodology concerns included the sources and quality of data, nonrandom missing information, data timeliness, and the need for different risk scores by population. Panelists also raised concerns about potential bias and misapplication of a polysocial risk score. CONCLUSIONS: A polysocial risk score is a potentially useful addition to the growing methodologies to better understand and address HRSNs. Nevertheless, development is potentially complicated and fraught with challenges.