Substance use and abuse, which includes alcohol use, alcohol dependence, drug use, and drug dependence, inflicts a substantial toll on Americans. Although studies have demonstrated the protective effect of social support, such as religious participation and via marriage, understanding their influence on racial and ethnic minorities is limited. Thus, the aim of this study is to assess the impact of social support on substance use and abuse in racial and ethnic minorities. The Collaborative Psychiatric Epidemiology Surveys, sponsored by the National Institute of Mental Health, a repository of race, ethnicity, and mental health data, was leveraged to develop four models using multivariate analysis, specifically logistic regression to estimate the probability of meeting the criteria for substance use and abuse. Racial and ethnic minorities were found to have lower rates of substance use and abuse compared to Whites, and foreign-born individuals were consistently less likely to use or abuse substances compared to American-born minorities. Mental health conditions were highly associated with substance use and abuse, and social support by way of religious participation and marriage was protective against substance use and abuse. In racial and ethnic minorities, nativity and social support were protective against substance use and abuse; however, these protective factors did not completely eliminate risk. Thus, although race and ethnicity are important to understanding health outcomes and health behaviors, such as substance use and abuse, it is the intersection of multiple factors, representing internal and external forces, which may be more informative and offer a more comprehensive picture of the landscape influencing drug and alcohol use and dependence. Targeted interventions should consider leveraging religious spaces and bilingual materials when attempting to reach racial and ethnic minorities.