Social determinants of health (SDoH) are the conditions in which people live and work that shape access to essential social and economic resources. Calls for healthcare systems to intervene on unmet social needs have stimulated several large-scale initiatives across the country. Yet, such activities are underway in the absence of a unifying conceptual framework outlining the potential mechanisms by which healthcare-based unmet social need interventions can improve health outcomes. Drawing on theoretical foundations and empirical evidence about the relationship between unmet social needs and health, the authors developed the OASIS (Outcomes from Addressing SDoH in Systems) conceptual framework to map the known and hypothesized pathways by which unmet social need screening and referral interventions may impact outcomes. The OASIS framework may help guide policy makers, healthcare system leaders, clinicians, and researchers to utilize a more unified approach in their efforts to implement and evaluate unmet social need interventions and thus foster the development of an evidence base to inform healthcare systems to more effectively mitigate the consequences of unmet social needs. Adopting an overarching conceptual framework for addressing unmet social needs by healthcare systems holds promise for better achieving health equity and promoting health at the individual and population levels.