Background and Purpose: Drug use among university students, as a serious social issue, poses a significant threat to their mental health, academic performance, and future prospects. The present study aims to identify the multidimensional factors influencing the prevalence of drug use among students across the country. Method: This qualitative study employed a systematic meta-synthesis approach based on Sandelowski and Barroso’s (2007) model. The statistical population consisted of 134 domestic studies conducted between 2001–2024. After applying inclusion criteria, 97 relevant and methodologically valid studies were selected and analyzed. Data were analyzed using axial and selective coding techniques. Findings: According to the findings, the prevalence of drug use occurs within the context of five major social factors: (family disruption, social capital crisis, differential association, easy access to drugs, weakness of social control mechanisms, and social anomie), economic factors (economic deprivation, unemployment, financial pressures, class inequality, wealth as status), cultural factors (deviant subculture, normalization of drug use, high-risk lifestyle, cultural poverty, weakness of counseling programs, harmful leisure activities, decline in religious attachment), psychological factors (emotional void, sense of alienation, identity crisis, individual curiosity, weak coping skills), and individual-contextual factors (history of use, young age, gender, place of birth, and field of study). Conclusion: To reduce drug use among university students, targeted interventions at the university level are essential. These should emphasize strengthening counseling services, enhancing social and emotional support for newcomer students, creating recreational and cultural spaces, providing long-term student loans, and fostering university-industry collaboration to promote students employment. Additionally, adopting security-oriented approaches such as increased campus surveillance and police-university cooperation to control drug access alongside community-oriented programs (e. g., psychological counseling, coping skills training, and cultural-sports activities to reduce sensation-seeking and resolve family conflicts) may significantly contribute to effective drug prevention.