Abstract Introduction The prescribing rate of Opioids is increasing and is perceived as main contributor to opioid misuse.1,2 Community pharmacists can help reduce opioid misuse rates by carrying out licit opioid misuse prevention services.3 Understanding and reviewing the barriers and facilitators to community pharmacists’ involvement in the prevention of licit (over-the-counter and prescription) opioid misuse prevention services have the potential to significantly improve these services. Aim To identify, collate and synthesise existing evidence of stakeholders’ views regarding barriers and facilitators to community pharmacists’ role in licit opioid misuse. Methods A systematic review of original studies was carried out in MEDLINE, Embase, Scopus, Web of Science, CINAHL, and APA PsycINFO using search terms for community pharmacy, opioid misuse interventions and opioid misuse. Titles, abstract and full text were independently reviewed by two researchers and consensus on eligibility of included studies was reached. Studies were included if they were: either qualitative or mixed methods studies of community pharmacy and licit opioid misuse; published in English; either over-the-counter or prescription opioids. Quantitative, non-English studies; and studies on illicit opioids were excluded. Narrative synthesis was carried out by: developing a theory of change model, data extraction and thematic analysis, discussing relationship and robustness of studies. Quality assessment was carried out by the Joanna Briggs Institute critical appraisal checklist. Ethical approval was obtained from Newcastle University Faculty of Medical Sciences Research ethics committee. Results A total of 1,234 articles were retrieved from all database searches. After deduplication, title, abstract screening and data extraction, 10 studies were included. Barriers and facilitators identified are knowledge and skill, pharmacists’ attitude, relationship with prescribers, time, number of support staff, remuneration of service, scheduling of over-the-counter opioids, corporate pharmacy support, private counseling room and electronic programmes. The factors grouped as: capabilities are knowledge and skill; opportunities include relationship with prescribers, time, number of support staff, remuneration of services, scheduling of over-the-counter opioids, corporate pharmacy support, private counseling room and electronic programmes while motivation was Pharmacists’ attitude. Discussion/Conclusion Overall, Study opines that: (1) improving capabilities and opportunities will improve motivation of the Community Pharmacists; (2) improved motivation of Community Pharmacists will improve their involvement in the prevention of licit opioids misuse. (3) Improved capability could be achieved by implementation of policies that focus on: improving opioid misuse education at the undergraduate level and routine training of community pharmacists; while (4) improved opportunity could be achieved by implementing integrated pharmacy care model (a health system in which community pharmacists and prescribers collaborate), increased number of pharmacy support staff, remuneration for service, upscheduling of OTC opioids, pharmacy managers’ support, modifying the community pharmacy setting to include a private consultation area and efficient electronic systems. Findings of this study may not be generalized to developing countries because majority of the studies included in the review were carried out in developed countries. However, implementation of these factors (by policy makers, pharmacy managers) will improve community pharmacists’ attitude towards the provision of licit opioid misuse prevention services resulting in improved community pharmacists’ involvement in these services.