The study has focused on four types of substances (namely: Khat, Cigarette, Alcohol and Shisha) use among high school students. Both the current and life time prevalence of each substance use was determined. A multi-stage proportional sampling technique was used in order to identify the statistically determined sample size from the study population. A mixed (quantitative and qualitative) study design was employed in order to come up with reliable findings regarding determinants of each substance use. In addition, the study also utilized a standardized data collection tool which was guided by the conceptual framework. The multivariate analysis has provided important determinant factors for each substance uses. The Focus Group Discussions held have also provided with pertinent determinants of each substance uses.