The rise in the prevalence of substance use among adolescents has triggered researchers for more studies on substance use and intervention strategies. The aim of the review is to provide a synthesis of effective preventive strategies in the face of multiple and variant literature on adolescent substance use data. A Google Scholar, and PUBMED academic literature published in English from 2012 to 2022 were included. A Google search of Keywords for the search were adolescent, substance use and preventive strategies. The described principles of prevention science provide examples of efficacious preventive interventions. It describes challenges and potential solutions necessary to take efficacious prevention policies and programs. It tends to scale and conclude with recommendations on how to reduce the burden of adolescent substance use mortality and morbidity worldwide through preventive interventions. Effective strategies share common goals with strengthening ‘protective factors,’ such as well-developed social skills, strong family bonds, attachment, active involvement, community, and religious organizations, while reducing ‘risk factors’ that increase vulnerability to substance use. In conclusion, several strategies are positive and effective, while some lack acceptable evidence for interventions. These attributes can help resource-constrained nations mount effective control measures against substance use. Keywords: Adolescence; Intervention; Substance Use; Strategies.