Over the years, substance abuse has been a major challenge in Tai Solarin University of Education, Ijagun, Ogun State, Nigeria. Some of the reasons for substance abuse among undergraduates include family upbringing, ceremonial exposure, insecurity, anticipation, sex drive and festival usage. Substance abuse among undergraduates caused property damage within educational institution and diminishes the prospects of academic success of undergraduates. While examining the cultural factors that influence substance abuse among undergraduates of Tai Solarin University of Education in Ogun State, a descriptive survey research design was employed. The study utilized a simple random sampling technique to select a sample of eight hundred (800) undergraduates. The researcher used statistical tools such as frequency counts, percentages, and chi-square tests at a significance level of 0.05. The analysis resulted in the rejection of all three hypotheses. The study identified festival, ceremony and religion as significant contributors to substance abuse among Tai Solarin University of Education undergraduates. The study recommends mandatory medical tests for substance abuse at all undergraduate levels and advocates active involvement of health educators in educating students.