Unmet social needs (e.g., housing instability, food insecurity, transportation barriers) impact a patient's ability to participate in health-seeking behaviors (e.g., physical activity, routine preventive care) and to achieve optimal health. A rapidly growing number of health care systems are incorporating social needs screening and assistance into clinical workflows, yet many implementation and sustainability challenges exist and require collaboration with social service organizations. This review highlights implementation approaches used within this rapidly changing US landscape and uses implementation science frameworks to systematically identify multilevel barriers to and facilitators of implementing and sustaining social needs care. Policies and economic investments are necessary as they determine critical barriers and facilitators within the clinical and social service contexts. Implementation may be further strengthened by cross-sector engagement, evidence-based implementation strategies, and capacity building within clinical and social service organizations. Successful, sustained implementation of social needs care may improve the quality of health care, population health, and health equity.