BackgroundWe assessed sociodemog. variables, risky determinants, and type of drug use associated with fatal overdose among people who use drugs (PWUD). MethodsStudies in English published from Jan. 1, 1985 to May 1, 2021, were searched on PubMed, Scopus, Cochrane, and Web of Science to identify studies on variables associated with fatal overdoses among PWUDs. After reviewing for study duplicates, the full-text of selected articles were assessed for eligibility using Population, Intervention, Comparator, Outcomes (PICO) criteria: (i) population: PWUD; (ii) intervention: fatal overdose in the past year; (iii) comparator: PWUD who had not fatal overdose; (iv) outcome: fatal overdose in the last year and (v) study type: cross-sectional, cohort, and case-control studies. ResultsOut of 13,821 articles, 25 studies met eligibility criteria. Our findings showed socio-demog. determinants (younger age, marital status, being homeless, being male,) risky determinants (poor mental health, experience non-fatal overdose and needle sharing), and type of drug use (cocaine disorder, benzodiazepines disorder, alc. disorder, psychostimulant disorder, polysubstance disorders, and heroin dependence), were significantly associated with fatal overdose among PWUD. ConclusionsThe present study data indicated that numerous characteristics were correlated with overdose-induced mortality. Such characteristics are certainly interrelated; however, each factor could potentially be targeted for intervention. The most particular reason for death was practicing illicit drug use, including opioids (e.g., heroin). AbbreviationsPWUD: People who use drug; CI: Confidence intervals; NOS: Newcastle-Ottawa Scale; OR: Odds ratio; PICO: Population, Intervention, Comparator, Outcomes; PRISMA: Protocols of Systematic Reviews and Meta-Analyses; PWIDs: People who inject drugs; WHO: World Health Organization