Quality improvement (QI) focused on the review and refinement of outreach materials is important for enhancing Indigenous health care. Here, a health literacy QI project is described involving the incorporation of Indigenous knowledge into cancer prevention outreach materials. Indigenous peoples face some of the greatest health disparities globally, including increased rates of cancer diagnoses at later stages and higher mortality rates than the general population. Student interns from a US National Cancer Institute (NCI)-designated cancer center and Canadian University shared responsibility in working with Indigenous first-language speakers over multiple summers to improve messaging. For Indigenous populations, usable, visually appealing, and culturally sensitive information are key to communicating important messages. Outreach materials then underwent elder review, creating new language definitions for use in English-to-Indigenous language adaptations. Next, the cancer center’s creative service team produced revised materials incorporating recommendations. Finally, the materials were presented back to Black, Indigenous, People of Color (BIPOC) urban community groups and allies. Reviewers noted the importance of community-friendly language and incorporation of Indigenous language. Increased use of Indigenous-based cancer statistics and delivery of Indigenous-adapted materials back to health systems, urban centers, and community-based organizations were recommended. These experiences offer an exemplar to strengthen tribal programming.