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This study investigates the impact of personal and environmental factors, with greater emphasis on the impact of religiosity on alcohol and marijuana use (Ys) among white, African American, and Asian American adolescents. Specifically, this study aims to (1) examine if the parental influence, peer influence, religiosity, and school-based prevention programs independently and significantly predict the Ys, controlling for background factors; (2) explore whether or not the expected impact of religiosity on Ys is qualified by race, gender and age; and (3) explore if religiosity acts as a mediator of the relationships of age, race and gender with alcohol and marijuana use. This study hypothesizes that (1) religiosity, school-based prevention programs, parental support, parental monitoring, parental disapproval, peer use, and peer disapproval will together significantly explain alcohol and marijuana use; and (2) higher religiosity, attending alcohol and drug training programs, higher parental support, higher parental monitoring, parental disapproval, peer disapproval, and less peer use will independently and separately be related to lower likelihood of marijuana and alcohol use, controlling for background factors. The scope of this study aims at White, African American, and Asian American adolescents aged 12 to 17 years old. A total of 12,984 adolescents were computed from the 2013 National Survey on Drug Use and Health (NSDUH) data. Separate binary logistic regression analyses were conducted to examine the impact of individual religiosity, parental influence, peer influence, and school-based prevention programs on alcohol and marijuana use among the study participants. Also, combination of OLS regression analysis and binary logistic regression analyses was used to explore the moderation and mediation effects of religiosity, age, race, and gender on alcohol and marijuana use among the study participants. Findings confirm the study hypotheses. Results of exploratory analyses reveal that religious girls are less likely to use alcohol and marijuana than religious boys; religiosity is not impactful on alcohol and marijuana use among Asian American youth, which needs further investigations; and religiosity can serve as a mediator on alcohol and marijuana use among African American youth and female adolescents. Implications for social work practice, future research, and drug policy are also discussed.