Substance use among youths is an increasing global challenge, particularly in urban areas of developing countries. Out-of-school youths are considered a highly vulnerable population due to their exposure to social, economic, and environmental risks. In Kano Metropolis, rising unemployment, peer influence, street life, and availability of psychoactive substances such as cannabis, tramadol, codeine mixtures, inhalants (e.g., solution, glue), and other locally prepared stimulants have contributed to increased experimentation and habitual use among this group. Being out of school reduces protective factors such as structured learning environments, adult supervision, and career prospects, placing youths at heightened risk of substance initiation and dependency. Understanding the determinants of substance use among this population is essential for developing effective prevention, rehabilitation, and policy strategies. The male out of school youths abuse drugs mainly to do something un-usual while females abuse drugs due to friend influence. Factors associated with drug abuse for males are mainly peer group influence and relapse while that for females are lack of parental support and family care among these predisposing factors are influences to start abusing, influences to continue abusing, influences to stop abusing and influences to relapse back to abusing drugs The continues/relapse factors for substance/drug abuse for males is mainly environmental influences, while for females is peer group influences. A population of 463 out of school youths were taken from eight local governments in Kano metropolis, 257 males and 206 females. The minimum age of the respondents were 18years and maximum age of the respondents were 29 years. A multistage sampling technique was used to collect data using an adapted interview administered semi structured questionnaire, SPSS Version 24 was used to analyse the data.