Background: Screening and brief interventions (SBI) can help identify opioid safety risks and healthcare professionals can accordingly intervene without a significant increase in workload. Pharmacists, one of the most accessible healthcare professionals, are uniquely positioned to offer SBI. To design an effective intervention with high potential for implementation, we explored pharmacist needs and barriers regarding SBI for opioid use disorders. Methods: Using the Consolidated Framework for Implementation Research (CFIR), we conducted 11 semi-structured 60-minute interviews with community pharmacists. We used a purposeful sample of English-speaking pharmacists practicing in varied pharmacies (small independent, large-chain, specialty-retail) and positions (managers, owners, full-time/part-time pharmacists). Transcriptions were analyzed using deductive content analysis based on CFIR constructs, followed by inductive open coding. Utilizing a theoretical framework for data collection and analysis, a diverse sample of pharmacist roles, peer debriefing, and 2 independent coders for each transcript, altogether increased the credibility and transferability of our research. Data collection and analysis continued until data saturation was achieved. Results: Pharmacists described good working relationships with colleagues, organization cultures that were open to new initiatives, and believed the SBI to be compatible with their organization goals and pharmacy structure, which are facilitators for future SBI implementation. Pharmacists were motivated by improved patient outcomes, more patient interaction and clinical roles, representing facilitators at the individual level. They also described stigma toward patients, mixed need for change, and lack of knowledge regarding SBI, which are potential barriers to be addressed. Pharmacists believed that the SBI model was adaptable, not complicated, and benefits outweighed implementation costs. Conclusions: We addressed current SBI literature gaps—mainly lack of focus on implementation and contextual data, through rigorous implementation-focused qualitative research. Our exploratory findings have direct implications on future pharmacy-based SBI implementation.