Many current theories guiding substance abuse prevention (SAP) programs stem from Western ideologies, leading to a scarcity of research on theories from, and a disconnect with, Indigenous perspectives. This qualitative research study explored perceptions of theory by SAP researchers (N = 22) working with American Indian and Alaska Native communities. In-depth interviews identified components of Indigenous theoretical perspectives, including cultural elements such as balance, social cohesion, and belonging as being particularly significant and currently absent from many SAP programs. Recommendations for conducting metatheory studies and operationalization of Indigenous perspectives into guiding theoretical underpinnings for future SAP programming are provided.