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This study examines the complex relationship between academic pressure and illicit drug use among adolescents in the Greater China region, focusing on three distinct urban areas: Shanghai, Macau, and Taipei. Utilizing Agnew’s general strain theory as the theoretical framework, the research explores how academic pressure influences adolescent drug abuse. The findings reveal a positive correlation between academic stress and drug use across all three cities. Furthermore, the study highlights the moderating role of city residency, showing that increased academic pressure has a more pronounced effect on drug use among adolescents in Macau and Taipei than those in Shanghai, though subtle differences remain between the two regions. The research emphasizes the need for interventions tailored to each city's unique educational systems and social norms. It also recommends that future studies adopt longitudinal approaches and consider diverse social contexts to gain a more comprehensive understanding of these dynamics.