Substance use is a common issue worldwide, but it disproportionately affects the Indigenous population in America. As culture affects many aspects of health and wellness, including the presentation and effectiveness of treatment interventions, it is vital that health care providers look at substance use within a cultural context. The Campinha-Bacote Model: The Process of Cultural Competemility in the Delivery of Healthcare Services model is a helpful tool to assess a cultural group in the context of health care. The knowledge and use of this model may assist health care professionals in providing culturally competent care for the Indigenous population in America, as well as other people from various cultural backgrounds. This model also promotes the consideration of cultural factors in nursing research and evidence-based interventions, which may assist in reducing the current disparities that exist within the Indigenous population. The current article addresses the Campinha-Bacote Model in reference to substance use disorder in the Indigenous population in America and the relation to nursing practice and research. [Journal of Psychosocial Nursing and Mental Health Services, 59(6), 7-12.].