The harmful or hazardous use of substances including illegal drugs, prescription medications used non-medically, alcohol, and inhalants is known as drug abuse. Males tend to have a higher prevalence and more varied substance use, often starting at a younger age than females. Drug abuse is emerging as a global public health issue. Youth are more vulnerable because their brains are still developing, which makes drug use potentially more harmful. Early drug exposure may lead to addiction, poor academic performance, risky behavior, and mental health issues. The aim of this study is to Evaluate and compare the prevalence and types of substances commonly abused by male and female out of school in Kano metropolis. This study was a cross-sectional study that assesses and compares the pattern of substance abuse among males and females out of school youths in Kano metropolis. A total of 463 (257 males and 206 females) out of school youths were taken from eight local governments in Kano metropolis, with age between 18 and 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. The study revealed that the substances abuse by males and females out of school youths in Kano metropolis includes: alcohol, cigarette and shisha, marijuana, syrups and tramadol, among others while males commonly abuse cigarette and shisha the female, abuse more of syrups. The male out of school youths abuses drugs mainly to do something un-usual while females abuse drugs due to friend influence.