The current opioid overdose crisis is significantly influenced by the evolving dynamics of drug markets, with fentanyl emerging as the predominant opioid in North America. Chronic pain remains a key driver of prescription opioid use among drug-using populations worldwide. This review examines the association between opioid misuse and chronic pain, particularly the transition from other prescribed analgesics to unprescribed fentanyl for pain management. We conducted a systematic review of literature from MEDLINE, CINAHL, Web of Science Core Collection, and PsycInfo using a combination of keywords, medical subject headings (MeSH), and Non-MeSH terms such as “fentanyl,” “chronic pain,” and “misuse.” All papers that described unprescribed fentanyl use to treat pain were included. After screening, 16 studies remained, including case studies, qualitative studies, observational cross-sectional studies, and retrospective observational studies. Findings indicate that motivation for street fentanyl use often stemmed from a lack of sufficient pain management from prescribed medications. The stigma surrounding opioid prescriptions emerged as a major barrier; patients expressed shame when requesting higher doses of opioids, and providers were hesitant to prescribe them. One limitation of this review is the small number of included studies and the heterogeneity of study designs, which may limit generalizability. Overall, our review found that un- or undertreated chronic pain is a critical reason fueling the shift toward fentanyl use in the current overdose crisis. Improvements in access to qualified pain treatment and targeted training for clinicians in opioid stewardship and pain monitoring may help reduce the number of street opioid users.