This study investigated the psychosocial factors influencing substance abuse among undergraduates. The study was conducted in Ekiti State university Ado Ekiti. 150 participants who are undergraduates of the university were used in this research. They consist of 82 males and 68 females selected from all faculties in the institution. 3 questionnaires were administered to respondent to measure the factors influencing substance abuse and the level at which they are abused. Independent T-test, multiple regression and Pearson Correlation method were used to analyze the data collected. Five hypotheses were tested: hypothesis 1, 2, 3 and 4 were significant while hypothesis 5 was insignificant. It was observed that there was significant influence of religiosity on substance abuse among undergraduates, the result also revealed that there was a significant influence of self-esteem on substance abuse among undergraduates, it also revealed that religiosity and self-esteem jointly predicted substance abuse among undergraduates, likewise the result also show that there was significant influence of sex on substance abuse among undergraduates and finally the result revealed there was no significant relationship between religiosity and self-esteem among undergraduates. The results were discussed in line with relevant empirical literatures, while conclusion and recommendations subsequently followed.