<p>Alcohol and substance use (A/SU) during pregnancy is intertwined with social determinants of health, adverse childhood experiences (ACEs), and intimate partner violence (IPV). All of these risks disproportionately impact American Indian/Alaska Native (AI/AN) people; however, we have limited research on how these risks relate to prenatal A/SU among AI/AN or potential protective factors. Utilizing survey (n = 99) and focus group (N = 5) data collected from an urban area in the northern plains region of the U.S., this study applied chi-square and Mann-Whitney U tests for evaluating associations between A/SU during pregnancy and risk/protective factors including IPV, ACEs, support systems, and cultural identity, values and traditions. Focus group data were analyzed using directed content analysis to verify and expand on associations, with joint displays enabling a comprehensive comparison of mixed methods results. Both quantitative and qualitative findings indicated that exposure to IPV, parental substance use, and ACEs increased the risk of prenatal A/SU among AI/AN individuals. Although not evident in quantitative findings, social support, cultural values, AI/AN identity, and traditions were described in qualitative data as protective against prenatal A/SU risk. Finally, healthcare/western medicine, as an inductive theme, revealed that current practices in western medicine often deter AI/AN birthing people from seeking prenatal care. There were differences in survey measures and how similar factors were discussed qualitatively, which provided a more robust understanding of how cultural and spiritual traditions are experienced by AI/AN individuals. These findings have implications for how healthcare considers cultural and spiritual resources.</p>