Rural adolescents are more likely than their peers in urban areas to engage in high-risk substance use, including opioid misuse. Rural adolescents also face challenges accessing behavioral care because of limited clinics and providers in rural settings, including substance use care providers. External specialists may fill a critical gap in augmenting existing school-based services; however, challenges in cross-system coordination contribute to poor reach and retention in care. These challenges are particularly urgent given the need to treat opioid use disorder (OUD) and prevent escalation to OUD among high-risk adolescents with other substance use disorder (SUD) or behavioral health challenges. Research is needed to identify implementation strategies that support cross-system coordination without overburdening existing school staff. The proposed K23 will examine the implementation and effectiveness of an innovative community partnership-the Youth Substance Use Unit (YSU), a collaboration between schools and local substance use service providers that delivers services to adolescents with substance use problems at high schools on the rural Eastern Shore of Maryland. Guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, the study has three aims: (1) identify determinants and opportunities to improve implementation of the YSU by conducting semi-structured interviews with constituents (e.g., school personnel, peer recovery specialists); (2) develop and adapt initial implementation strategies to improve reach and implementation of the YSU into rural schools based on constituent feedback using Implementation Mapping, a participatory approach to co-develop and specify implementation strategies; and (3) test the effectiveness and implementation of the YSU in Type 2 hybrid effectiveness-implementation trial using an adaptive-iterative design. Support for this trial is provided by the HEAL Initiative (https://heal.nih.gov/).