Missouri’s metropolitan areas—St. Louis, Kansas City, Columbia, and Springfield—propose establishing a multijurisdictional Opioid Community of Practice (OCP). The proposed project will achieve the following goals: (1) collaborate to improve identification, collection, and utilization of opioid data; (2) prioritize and enhance community-based interventions and system-level strategies using improved opioid data and collective action that address social determinants of health; and (3) leverage action researchers, local public health entities, and regional data collaborative groups to evaluate the collective impact of the learning community and the impact of resulting interventions on reducing opioid misuse. The Missouri Institute of Mental Health at the University of Missouri–St. Louis will serve as the project’s research partner.