This systematic review examines the association between area-level socioeconomic disadvantage measures, specifically the Area Deprivation Index (ADI) and Social Vulnerability Index (SVI), and health care spending in the United States. The review included 24 cross-sectional, case-control, and cohort studies published between 2020 and 2023. The findings suggest that higher ADI and SVI are associated with increased health care spending, with adjusted models showing increases ranging from $574 to $24,075 for various health care outcomes. The mechanisms underlying these associations include postoperative complications, readmission risk, and poor primary care access. The review highlights the importance of incorporating area-level measures into payment and care delivery programs to address social risk and improve access to high-value care for marginalized communities. However, the review also notes limitations, such as the need for more granular data and the potential for inequities within larger geographic areas. Overall, the findings suggest that ADI and SVI can play crucial roles in understanding drivers of health care spending and designing equitable payment and care models.This systematic review examines the association between area-level socioeconomic disadvantage measures, specifically the Area Deprivation Index (ADI) and Social Vulnerability Index (SVI), and health care spending in the United States. The review included 24 cross-sectional, case-control, and cohort studies published between 2020 and 2023. The findings suggest that higher ADI and SVI are associated with increased health care spending, with adjusted models showing increases ranging from $574 to $24,075 for various health care outcomes. The mechanisms underlying these associations include postoperative complications, readmission risk, and poor primary care access. The review highlights the importance of incorporating area-level measures into payment and care delivery programs to address social risk and improve access to high-value care for marginalized communities. However, the review also notes limitations, such as the need for more granular data and the potential for inequities within larger geographic areas. Overall, the findings suggest that ADI and SVI can play crucial roles in understanding drivers of health care spending and designing equitable payment and care models.