This article reviews and synthesises findings from studies on non-medical use of prescription opioids (NMUPO) and new psychoactive substances (NPS) in Nigeria. PubMed, EBSCO, Ajol and Google scholar were searched for relevant literature on NMUPO in Nigeria from February 2000 to January 2022. Articles were included if they collected primary data, were published in English, and reported the prevalence rate, motivation, or source of prescription opioids for non-medical use and NPS in Nigeria. The search result yielded 152 relevant articles after duplicates were removed and 49 articles were included in the final review. The findings reveal that tramadol and codeine-containing cough syrups (CCCS) are the most commonly used prescription opioids for non-medical purposes. The current use of CCCS and tramadol was high among young people in university and secondary school. Common motivations for NMUPO use were availability, peer pressure and enhancing physical work performance. Major sources of tramadol, codeine and CCCS for non-medical use were retail drug dealers, chemists/pharmacy stores and wholesale drug dealers. The NPS reported and used by young adults include Solution, Madaran Sukudie, Dan kamaru, and Gadagi, and drug concoctions such as Codeine diet, Gutter water and Monkey Tail. Although codeine and tramadol are among the Controlled Medicines in Nigeria, the findings support the need to implement tailored policies to mitigate an opioid crisis in Nigeria.