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Substance abuse among university students is a significant public health concern that is typically linked to underlying mental health issues such as depression, stress, and a lack of social support networks. Thus, the study's goal was to investigate the link between social support, depression, and substance abuse. A cross-sectional design was used. Students were given 3 measures to complete for the current study: the Multidimensional Scale of Perceived Social Support, the Beck Depression Inventory, and the Alcohol, Smoking, and Substance Involvement Screening Test. The study included 257 regular undergraduate students from Addis Ababa Institute of Technology. As a result, the multivariate test of significance demonstrates that parents' marital status, monthly income, and the presence or absence of intimate friends all have a significant influence on student substance abuse and depression. The Pearson correlation demonstrated a substantial positive relationship between depression and substance abuse; however, higher levels of social support are associated with a decreased likelihood of substance abuse and depression among students. Finally, depression has a mediating role in the relationship between social support and substance abuse. These findings suggest that investing in supportive relationships and communities might be an effective way to improve mental health while simultaneously lowering risky behavior like substance abuse. Furthermore, the researchers proposed that the institution establish its own substance abuse prevention and treatment center, available to psychologists, therapists, and other health practitioners.