Native American students face significant challenges in higher education, including lower enrollment, persistence, and graduation rates compared to other ethnic groups. Many of these students are first-generation and non-traditional learners, often balancing work and family responsibilities while navigating systemic barriers rooted in historical trauma, financial instability, and cultural dissonance within mainstream academic institutions. Tribal Colleges and Universities (TCUs) play a crucial role in addressing these disparities by providing culturally relevant support systems that foster student success. This mixed-methods study explored best practices for TCUs to enhance academic success among first-generation Native American students. Through surveys with faculty, staff, and students at three TCUs, the research identifies key strategies that improve retention and completion rates. These include holistic student support services, culturally embedded curricula, mentoring programs, and streamlined institutional processes like one-stop support centers. Findings suggest that strengthening students' sense of belonging, incorporating Indigenous knowledge systems, and addressing financial and logistical barriers are critical to increasing academic success. The study's conclusions offer practical recommendations for TCUs to develop policies and programs that align with the unique needs of Native students. By implementing culturally responsive strategies, institutions can not only improve individual student outcomes but also contribute to the long-term empowerment of Native communities.