Context: Drug-related mortality is a major concern in public and global health discussions. Objectives: Therefore, the aim of this study was to investigate the prevalence, causes, and prevention of death after individuals are released from prison. Methods: This study was conducted systematically using MeSH keywords with no language or time restrictions. PubMed, Scopus, and Web of Science databases were extensively searched for observational studies from 1980/1/1 to 2023/12/30, following the PRISMA checklist. Fourteen research studies were ultimately included in the systematic review process. The CRD code is CRD42024571756. Results: The two-week period following release, with an 18% prevalence, was identified as the time when most overdose deaths occurred. The leading causes of death included prior heroin use, previous experiences with drug withdrawal, drug injection, and sedative use within six months before death. Compared to other unnatural causes of death, there was an increased risk of fatal drug overdose for individuals who died within the first two months of release. Men had higher death rates from all causes compared to women. Most studies reported that substance abuse treatment during imprisonment and providing take-home naloxone for emergencies protected against mortality from all causes. Conclusions: In conclusion, evidence from these systematic investigations highlights the urgent need for targeted interventions to address substance use disorders and overdose prevention among individuals recently released from prison. Efforts to bridge the gap between incarceration and community reintegration should prioritize comprehensive substance abuse treatment programs to reduce the heightened risk of mortality in this vulnerable population.