NIH held Tribal Consultations in 2018 and 2022 to seek input on research needs for addressing opioid misuse and improving pain management in Native communities. Many themes emerged, including the importance of Indigenous Knowledge and local expertise, and the need to invest in research and data led by Tribes and Native American Serving Organizations (T/NASOs). In direct response to priorities identified in Tribal Consultations, the Native Collective Research Effort to Enhance Wellness (N CREW) Program is a highly collaborative partnership between NIH, T/NASOs, and Ally Organizations established to directly respond to the opioid/drug public health emergency.