Cheema E, McGuinness K, Hadi MA, et al. - This article intended to systematically review the nature, causes, routes of administration, and toxicology of fentanyl-associated deaths applying case studies and case series in peer-reviewed published literature. Researchers carried out to search four electronic databases including Embase, Medline (via Ovid), Scopus, and Google Scholar from inception until October 2019 to distinguish the studies reporting fentanyl-related deaths. They applied the Joanna Briggs Institute quality assessment tool to assess the quality of included studies. In the included studies, a total of 1969 deaths were reported. The findings suggested that the literature related to fentanyl-associated deaths predominantly come from North America. The results demonstrated that the deaths are comparatively lower or not reported in peer-reviewed publications from the rest of the world. The outcomes suggested that abuse through intravenous administration, mixed drug toxicities, and self-treatment of breakthrough pain are mainly responsible for the majority of the reported deaths.