Youth involved in the legal system (YILS) experience rates of opioid and substance use disorders (OUD/SUDs) and overdose that is well above those in the general population. Despite the dire need, and the existing programs that focus on treatment of these problems in YILS, research on opioid initiation, and OUD prevention, including feasibility and sustainability, are severely limited. We present four studies testing interventions that, while not necessarily novel as SUD treatments, test novel structural and interpersonal strategies to prevent opioid initiation/OUD precursors. We discuss early implementation barriers and facilitators, including complexities of prevention research with YILS and adaptations due to COVID-19. We conclude by describing anticipated end products, including implementation of effective prevention interventions and integration of data from multiple projects to address larger, multi-site research questions.