This resource provides a framework for managing individuals with opioid use disorder (OUD) and co-occurring psychiatric conditions, such as mood, anxiety, and psychotic disorders. It emphasizes the foundational principle that medications for opioid use disorder (MOUD) are evidence-based and should be initiated or continued even when significant psychiatric comorbidities are present. The guide outlines a phased diagnostic approach prioritizing safety and stabilization while advocating for an integrated care model that combines behavioral health, pharmacotherapy, and social supports. Ultimately, the resource offers practical intervention strategies and tips for complex scenarios to improve patient retention and reduce the risk of overdose.