Context: The abuse of psychoactive substances which is one of the most important global public health problems begins in adolescence. Adolescents usually start by abusing the gateway substances. They suffer social, economic, physical, and legal consequences on account of use of substances, and this is very worrisome because of the increasing prevalence of use. Aims: The aim was to identify the characteristics of adolescents that use gateway substances. This knowledge shall be utilized in preventive programs. Settings and Design: Cross-sectional study with secondary school adolescents as participants. Subjects and Methods: Multistage sampling technique was used to select 492 respondents and the questionnaire consisted of characteristics of the adolescents, their families and schools and the alcohol, tobacco, cannabis, and stimulant use sections of the World Health Organisation questionnaire for student drug use surveys. Statistical Analysis Used: The data were analyzed using the Statistical Package for Social Sciences, and Chi-square statistics was used. Results: Having a friend who uses substance was significantly associated with tobacco, alcohol, cannabis, and caffeine use while being a male, having a family member that uses substance were significantly associated with tobacco, alcohol, and caffeine use. Older age, lack of satisfaction with the relationship with the teacher and polygamous family background were significantly associated with tobacco use. And finally, lack of satisfaction with the relationship with parents/guardians and having parents or guardians who are not religious were significantly associated with alcohol use. Conclusion: A comprehensive approach is needed to prevent the use of substances; this should target individuals, schools, families, and religious institutions.