Substance use is a major public health concern, and it may be correlated with mental health problems and inadequate social support. Youths who do not receive early intervention may be at high risk for substance use. The purpose of this study is to assess the correlation between mental health problems and substance use as well as substance use and social support among middle school and high school students, using secondary data from Maine Integrated Youth Health Survey. Logistic regressions were used to assess the correlation between the variables that measured substance use, social support, and mental health problems. The results showed that there was a statistically significant correlation between mental health problems and substance use as well as between substance use and social support among youths who are in middle and high school. By evaluating the correlation among substance use, mental health problems, and social support in middle school and high school students, focused interventions may be developed by providers and teachers to prevent substance use among youths.