Substance use disorder (SUD) is a multifactorial affliction influenced by personal choice, psychological factors, individual genetics, as well as by the user’s environment (Hawkins et al., Psychol Bull 112(1):64–105, 1992; Gilvarry and McArdle, Dev Med Child Neurol 49(8):636–640, 2007)—the latter being “social determinants” of substance use. Factors such as poverty, neighborhood environment, education level, social networks, employment, and healthcare access, all are social determinants that can affect the initiation, habitual use, treatment, and treatment outcomes of SUD. In this chapter we will explore the effects these social determinants of health (SDoH) have on SUD, highlighting the need to understand the intersectionality of SDoH—the complex interaction of these factors that is vital to understanding their impact on SUD and vital to creating a holistic approach to prevention and intervention. Of note, the Healthy People 2030 Initiative organizes SDoH into five domains: economic stability, education access and quality, healthcare access and quality, neighborhood and built environment, and social and community context.