States, payers, and health systems across the United States are developing cross-sectoral solutions to address health-related social needs. However, most evidence on the effectiveness of these interventions to date is from time-limited interventions focused on specific subpopulations or services and often in urban areas only. In 2019, as part of North Carolina’s Section 1115 Medicaid Demonstration, the Centers for Medicare & Medicaid Services (CMS) authorized up to $650 million in Medicaid funding to implement the Healthy Opportunities Pilots (“Pilots”). The Pilots, launched in 2021, is a cross-sectoral program providing 29 evidence-based services to address social needs related to housing, food, transportation, interpersonal violence, and toxic stress through networks of community-based organizations (CBOs) to eligible Medicaid enrollees in three regions of the state. The Pilots will test the impact of these interventions at scale in Medicaid for the first time, including through major new payment and delivery designs. An ongoing evaluation sponsored by CMS will examine the effect of the Pilots on health outcomes, health care utilization, and health care costs.