Objective: High levels of obesity-related health disparities are common among US American Indian (AI) populations. AI public university students often face unique challenges that may contribute to weight gain and related consequences. Few weight maintenance interventions have been developed that meet the needs of AI public university students. The goal of this study was to determine how to tailor Project Y.E.A.H. (Young Americans Eating and Active for Health), a web-delivered, weight maintenance tool developed for college students to make it culturally relevant for AI public university students. Methods: Three mini focus groups (N = 15) and five in-depth interviews (N = 11) were conducted with self-identified AI college students on the campus of South Dakota State University. Participants were recruited with assistance from the American Indian Education and Cultural Center and through campus publicity. Recorded sessions were transcribed and multistep coding was used to assess the aesthetic appeal of the website and determine variations of certain health-related factors. Results: AI public university students have specific and culturally influenced aesthetic, food and physical activity exposures and preferences. AI students may perceive unique stressors compared to non-AI students and practise cultural forms of stress relief. Conclusion: Specific and culturally relevant psychographic information regarding AI college student preferences is needed for the development of effective weight maintenance tools.