The drug overdose crisis in the United States continues to evolve, driven by overdose deaths involving synthetic opioids, often in combination with other substances, highlighting the need for adapting and innovating evidence-based prevention and response strategies.1 The Centers for Disease Control and Prevention (CDC) reports that 106 699 Americans died of drug overdoses in 2021, an increase of nearly 14% from 93 655 deaths in 2020.2 As public health leaders engage in the complex process of prevention on a population and individual basis, close strategic partnerships between public health and health care delivery systems have become increasingly important. Informatics innovation offers a timely and practical avenue to enhance these partnerships. For example, a recent publication3 on the West Virginia Prescription Drug Monitoring Program (PDMP) demonstrated the benefit of informatics innovation to support clinical decision-making and surveillance as vital components of that state's strategic partnerships that focus on the opioid overdose epidemic.