This article presents and discusses, in the new context of COVID-19, findings from a tabletop exercise on response and resilience in the ongoing opioid crisis in Pennsylvania. The exercise was organized by [identifying information removed] and held at the Pennsylvania Emergency Management Agency (PEMA), in further collaboration with the Governor’s Office of Homeland Security, the Pennsylvania Department of Health, and with the participation of several additional agencies and institutions. It addressed first-responder and whole-community response and resilience to the ongoing opioid crisis. More than 50 experts participated in the one-day program that involved state and local agencies, first-responder organizations, as well as academia in a discussion about effectuating comprehensive response to overdose incidents. Participant experts represented a wide array of backgrounds, including state and local law enforcement agencies; emergency medical technicians; public health and health care professionals; and scholars from the fields of law, security studies, public policy, and public health, among other relevant areas. Participants addressed specific challenges, including resource sharing among responders; capacity-building for long-term recovery; effective integration of non-traditional partners, such as spontaneous volunteers and donors; and public education and outreach to improve prevention. The exercise aimed to strengthen the whole-community approach to emergency response.