This convergent parallel mixed methods study based on Social Ecological Model investigated substance abuse among undergraduate university students at one of the universities in Ethiopia. For quantitative strand of study, data was collected from 422 randomly selected undergraduate students. Data were analysed using Statistical Package for Social Sciences version 17. For qualitative strand, face-to-face interviews were conducted with 17 purposefully selected participants directly involved with students abusing substances. The findings revealed that factors at individual, interpersonal, institutional, community and societal levels affect substance abuse among university students. The study also uncovered loopholes in the policies, guidelines, and programme implementations in the prevention, control, and management of substance abuse at the university. Based on the findings, the researcher developed guidelines based on the findings of the study, the critical literature review, and the inputs from the experts who reviewed the guidelines. The researcher assumes that implementation of the guidelines will reduce substance use and substance abuse among university students. / Health Studies / D. Litt. et Phil. (Health Studies)