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. The study analyzed 24 articles, including cross-sectional, case-control, and cohort studies, published between 2020 and 2023. The findings indicate that higher ADI and SVI are generally associated with increased health care spending, including claims-based spending and patient-reported barriers to care due to cost. Adjusted models showed that higher ADI or SVI residence was linked to increased spending for surgical hospitalizations, 30- and 90-day episodes of care, and total annual spending for Medicare beneficiaries. Postoperative complications, readmission risk, and poor primary care access were identified as key drivers of increased spending. The study highlights the importance of ADI and SVI in understanding drivers of health care spending and in designing payment and care delivery programs that account for social risk. However, the findings also reveal limitations, including the need for more granular data and the potential for ecological fallacy in using area-level measures to infer individual-level risks. The review emphasizes the need for equitable policies that consider the complex interplay of socioeconomic factors, health care access, and systemic inequities. The results suggest that area-level measures can inform interventions to improve access to high-value care and health promotion, particularly for historically marginalized communities. The study underscores the importance of addressing socioeconomic disparities in health care spending and access to ensure equitable health outcomes.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. The study analyzed 24 articles, including cross-sectional, case-control, and cohort studies, published between 2020 and 2023. The findings indicate that higher ADI and SVI are generally associated with increased health care spending, including claims-based spending and patient-reported barriers to care due to cost. Adjusted models showed that higher ADI or SVI residence was linked to increased spending for surgical hospitalizations, 30- and 90-day episodes of care, and total annual spending for Medicare beneficiaries. Postoperative complications, readmission risk, and poor primary care access were identified as key drivers of increased spending. The study highlights the importance of ADI and SVI in understanding drivers of health care spending and in designing payment and care delivery programs that account for social risk. However, the findings also reveal limitations, including the need for more granular data and the potential for ecological fallacy in using area-level measures to infer individual-level risks. The review emphasizes the need for equitable policies that consider the complex interplay of socioeconomic factors, health care access, and systemic inequities. The results suggest that area-level measures can inform interventions to improve access to high-value care and health promotion, particularly for historically marginalized communities. The study underscores the importance of addressing socioeconomic disparities in health care spending and access to ensure equitable health outcomes.