Substance use generates one of the greatest disability burdens in the world. The stigma associated with it results in myths and erroneous beliefs that hinder the care of people with such problems. Intersectionality is a paradigm that has been used in recent years to address the conditions of vulnerability in people who use substances. It incorporates the interrelationships of certain social determinants, among them gender, poverty, violence, ethnicity, and lack of access to health services. These refer to social inequities of a socioeconomic, political, and historical order that are of vital importance to understanding the processes of social exclusion of substance users in Latin America. Studies have shown some groups that share double or triple forms of exclusion, including those based on ethnicity (Hispanics, Latinos, and Blacks), gender (being a woman), sexual identity (LGTTBQ+), having a disability or a mental or physical condition such as HIV, being homeless, or being in prison. Our interest in this study is to contribute from an intersectional perspective to understanding the stigmatization of people who use substances, based on the review of international studies that have adopted this approach. We conclude by analyzing the importance of adopting an intersectional perspective to guide future interventions and support the development of public policy.