Children and adolescents are exposed to multiple contextual influences along their development towards adulthood. Before they transition to adulthood, adolescents acquire skills and knowledge usually in schools, which are one of the most influential contexts during adolescence. During school years performing well academically can generate better opportunities to become successful in the transition to adulthood. As part of their development, adolescents might face several challenging situations and eventually engage in non-conventional behaviors such as substance use. Research has shown that, during adolescence, academic performance and substance use are inversely related where it is difficult to distinguish between cause and effect. Thus, in this dissertation both outcomes are conceptualized as an inter-connected complex relationship. The literature has documented how several individual factors explain this relationship. However, how the school context influences this dynamic relationship has been scarcely investigated, leaving a research gap to be filled. To fill this gap, this dissertation uses a new conceptual model to explain the empirical findings related to school context effects on the dynamic between academic performance and substance use. The effects of these school factors were estimated, in a national representative sample of adolescents (ADD Health), using longitudinal and multilevel techniques--multilevel confirmatory factor analysis, multilevel conditional cross-lagged modeling. Two important findings: (a) the academic performance-substance use relationship is different depending on whether it is modeled at the student level (negative relationship) or school level (positive relationship); (b) three school context factors: a general risk factor, social and academic problems, and generalized academic pressure, had statistically significant effects on the relationship between academic performance and substance use. Theoretical implications rely on the importance to use more specific definitions of the school context. Policy and practical implications pivot around the idea that substance use and academic performance need to be understood as co-occurring outcomes. The findings provide empirical evidence suggesting that (i) educational and drug preventing programs need to integrate academic and social goals, aiming to prevent substance use while promote academic performance; and (ii) social and academic aspects of the school context need to be considered in framing intervention programs. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]