BACKGROUND: Prior studies have shown that virtual reality (VR) is an efficacious treatment modality for opioid-sparing pain management. However, the majority of these studies were conducted among primarily White, relatively advantaged populations and in well-resourced settings. OBJECTIVE: We conducted a qualitative, theory-informed implementation science study to assess the readiness for VR in safety-net settings. METHODS: Using the theoretical lens of the Consolidated Framework for Implementation Research (CFIR) framework, we conducted semistructured interviews with current VR users and nonusers based in safety-net health systems (n=15). We investigated barriers and facilitators to a commercially available, previously validated VR technology platform AppliedVR (Los Angeles, CA, USA). We used deductive qualitative analysis using the overarching domains of the CFIR framework and performed open, inductive coding to identify specific themes within each domain. RESULTS: Interviewees deemed the VR intervention to be useful, scalable, and an appealing alternative to existing pain management approaches. Both users and nonusers identified a lack of reimbursement for VR as a significant challenge for adoption. Current users cited positive patient feedback, but safety-net stakeholders voiced concern that existing VR content may not be relevant or appealing to diverse patients. All respondents acknowledged the challenge of integrating and maintaining VR in current pain management workflows across a range of clinical settings, and this adoption challenge was particularly acute, given resource and staffing constraints in safety-net settings. CONCLUSIONS: VR for pain management holds interest for frontline pain management clinicians and leadership in safety-net health settings but will require significant tailoring and adaption to address the needs of diverse populations. Integration into complex workflows for pain management is a significant barrier to adoption, and participants cited structural cost and reimbursement concerns as impediments to initial implementation and scaling of VR use.