A Human Well-being Index (HWBI) has been developed for the U.S. to help inform and empower decision makers to weigh and integrate human health, socio-economic, environmental and ecological factors equitably to foster sustainability. The integrity of the index structure is designed to be transferable to different U.S. population groups across space, time and demography. To demonstrate index transferability, American Indian Alaska Native (AIAN) specific data were evaluated for the calculation of a HWBI for AIAN and larger tribal populations. The applicability and integrity of the HWBI framework were maintained when using metrics scaled to assess well-being for AIAN and large tribal populations. Greater than 80% of the data available for a national AIAN assessment were specific to the target population, while the remaining data were derived from the general U.S. population. Full listings of domains, indicators and metrics for HWBI can be found in the U.S. Environmental Protection agency's report.