Substance use among youth is a significant public health concern with far-reaching implications for individual health and societal well-being. This review provides a comprehensive review of public health strategies aimed at preventing youth substance use, focusing on the examination of prevention programs and conceptual approaches. Prevention programs targeting youth substance use vary widely in their approaches, ranging from school-based interventions to community-wide initiatives. This review evaluates the effectiveness of different prevention programs, considering factors such as program structure, content, and duration. It highlights evidence-based programs that have demonstrated success in reducing substance use initiation and promoting healthy behaviors among youth. Moreover, the review discusses various conceptual approaches underpinning youth substance use prevention efforts. These approaches encompass socio-ecological models, which emphasize the influence of multiple levels of factors including individual, interpersonal, community, and societal influences on substance use behavior. Additionally, the socio-cultural perspective underscores the significance of cultural norms, beliefs, and values in shaping youth attitudes towards substance use. Furthermore, this review examines the role of policy interventions and regulatory measures in preventing youth substance use, emphasizing the importance of creating supportive environments and implementing evidence-informed policies to curb access to substances and minimize risk factors associated with youth substance use. In conclusion, effective prevention of youth substance use requires a multifaceted approach that integrates evidence-based programs, conceptual frameworks, and policy interventions. By addressing risk factors at various levels and promoting protective factors, public health strategies can play a pivotal role in reducing the prevalence of youth substance use and fostering healthier communities.