Background: Tobacco use among Bangladeshi university students is a major public health problem and often leads to illicit drug involvement. Growing evidence links early tobacco use with psychological distress and risky behaviors. This study aimed to examine how mental health challenges and social factors contribute to the transition from tobacco use to illicit drug consumption among university students in Bangladesh. Materials and Methods: This descriptive cross-sectional analysis was conducted using documented records and published literature from 2018 to 2022. Institutional data, national reports, and peer-reviewed studies were reviewed to assess the relationships between stress, peer influence, substance accessibility, and mental health outcomes. Data were coded and analyzed using SPSS and NVivo to identify quantitative patterns and thematic associations. Results: Findings from the reviewed sources showed that about 10% of university students were current tobacco users, and nearly 25% of them had experimented with illicit substances such as cannabis, cocaine, or methamphetamine. Mental health issues were highly prevalent, with approximately 60% experiencing anxiety, 45% reporting depression, and 30% indicating suicidal thoughts. Substance use was more common among male students (12%) and those from urban areas (12%) compared with female students (8%) and rural students (8%). Peer influence affected nearly 70% of students, while 65% identified academic stress as a major factor contributing to the initiation and continuation of substance use. Conclusion: This study highlights the interconnected roles of mental health distress, social influence, and environmental accessibility in the transition from tobacco to illicit drug use among Bangladeshi university students. Strengthening mental health support and implementing evidence-based awareness programs are essential to reduce substance-related risks in this population.