Background <p>Early recognition of substance use risk through contextual and behavioral indicators at first encounter is essential for guiding subsequent forensic procedures and safety measures.</p> Aim <p>To identify sociodemographic and external physical indicators that predict toxicologically confirmed illicit substance use in postmortem cases, aiming to inform structured risk-based triage models that enhance toxicological decision-making and occupational safety.</p> Methods <p>A retrospective case series was analyzed at a high-volume metropolitan forensic autopsy unit. Cases were systematically reviewed and coded using a dedicated forensic database to evaluate demographic factors, external examination findings, and toxicology outcomes.</p> Results <p>Illicit substance use was significantly associated with male sex, young adult age, injection marks, self-inflicted scars, and tattoos with criminological or substance-related themes. Although cachexia appeared more common among substance-positive individuals, the association was not statistically significant. The absence of key sociodemographic data (e.g., occupation, education) was noted as both a limitation and a potential indirect indicator of marginalization.</p> Conclusions <p>Several pre-autopsy indicators may support the early identification of individuals at elevated risk for illicit substance use, enabling more focused toxicological screening and stronger biosafety precautions. In routine forensic practice, where background data are often missing, and such absence may itself reflect elevated risk, a structured, observation-based triage approach can improve both diagnostic yield and occupational protection.</p>