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Adolescence is a phase of life between childhood and adulthood marked by rapid biological, social and psychological changes. During this phase, individuals bear a more emotional and curious mind and may engage in risky behaviours. Decades of investigations have revealed that substance use usually begins in adolescence. The main essence of this paper is to carry out an elaborative review of earlier works to recognize familiar risks and protective factors for substance use among adolescents at the global level. Additional emphasis was given to identifying the various statistical modelling approaches, widely used in earlier studies, to promote research methodological issues for future research in this specific domain. Articles published from 1991 to 2021 on adolescent substance use were downloaded, and after carrying out a preliminary full-text review, 50 articles were selected keeping the priority of the aforementioned objectives. After an intensive review, risk factors were identified and clustered around five broad domains such as individual, parental, familial, peer and environmental factors. Protective factors were also categorized under the headings of five broad domains viz. individual, parental, familial, social and interventional. Specific statistical modelling techniques were identified to evaluate the relative risk of specific groups of adolescents being in the clutches of substance use. It is necessary to recognise the potential risk and protective factors and their combined effect on substance use among adolescents to prevent this menace from society. For a better understanding of research about the exact vulnerable age of onset of …