BACKGROUND: Indigenous populations in the United States (US) experience worse health outcomes and higher disease prevalence compared to the US all race population. The World Health Organization (WHO), Canadian research on Indigenous-specific determinants, the Harvard Project on American Indian Economic Development, and the Native Nation's Institute have all identified governance as a determinant that impacts community health and development. This dissertation explored the active and potential role of Indigenous nations' governance, since the Native nation building era commenced in the 1970s, in protecting and promoting family and community health. OBJECTIVES: The dissertation aims were to: (1) describe the state of population data for US Indigenous nations and benefits of engaging with data, data sovereignty, and data governance for US Indigenous nations, (2) outline the history and current state of tribal public health relative to other US public health systems, and (3) elucidate the assumptions and applicability of the social determinants of health framework to Indigenous health contexts. METHODS: This mixed-methods study integrated retrospective quantitative and primary quantitative and qualitative data from case studies with six reservation-based American Indian tribes with qualitative data collected in a focus group and two consensus panels of public health practitioners and scholars. RESULTS: The results by aim were: (1) self-determination with regard to health and other population data offers Indigenous nations opportunities to create and access relevant and reliable data to inform policy and resource allocations, (2) the federal government and others have not invested in tribal public health authority infrastructures in ways similar to investments made in federal, state, and local public health authorities, resulting in tribal public health systems falling below other public health authorities in function and capacity, and (3) underlying Euro-Centric assumptions imbedded in the social determinants of health framework reduce its applicability in Indigenous health contexts. CONCLUSIONS: This study contributes to understanding the roles of Indigenous nation self-determination and sovereignty in defining health to align with Indigenous philosophies of wellness. Guided by Indigenous-specific determinants of health, tribes can set community-based, culture-informed methods and metrics for establishing, monitoring, and assessing public health policies and programs to support healthy communities and families. RECOMMENDATIONS: Indigenous nations, in partnership with researchers and other governments as appropriate, should develop framework(s) for tribal health that include broad, shared, and nation-specific definitions of health, healthy families and communities, and health determinants. Federal, state, and local governments should partner with Indigenous nations to improve tribal public health infrastructures and to support tribal data sovereignty and data governance through building tribal data capacity, aligning data with tribal self-conceptions, and forming data sharing agreements.