The misuse and abuse of substance by in-school adolescents has become a global issue and Nigeria is not exempted. The purpose of this study was to investigate the influence of substance abuse on psycho-social behaviour and academic performance of senior secondary school students in Ilorin Metropolis. Two research questions and two research hypotheses were answered and tested at 0.05 level of significance. The sample for the study comprised 220 SS1-3 students. The data collected were analyzed using mean, percentage and PPMC.