Support patients with pain, mental illness or a substance use disorder (SUD) by building an evidence-based, sustainable and resilient infrastructure and health care workforce rather than continuing a crisis-driven approach that has led to multiple unintended negative consequences, including one-size-fits-all strategies, continued stigma and widespread gaps in evidence-based treatment and prevention efforts. A renewed effort must be made to identify and support primary, secondary and tertiary SUD prevention efforts for children, adolescents and adults. This includes increased efforts to implement evidence-based strategies to address restrictions on care, overdose events and other harms experienced by patients with pain, mental illness or an SUD. Particular emphasis must be placed on collecting adequate, standardized data to eliminate inequities for historically marginalized and minoritized populations. Additional work must be done to address the increased complexity of access and treatment to SUD care as a result of the nation’s growing polysubstance use, overdose and death epidemic.