Identifying psychosocial strengths that support physical health can lead to better pathways to prevention and intervention. Relying on the resilience portfolio model as a conceptual framework, this study explores strengths in three domains (regulation, meaning making, and interpersonal) to identify promising protective factors to support physical health-related quality of life (P-HRQOL), controlling for prior exposure to adversity, age, and gender. This study uses data from four resilience portfolio model studies collected in the southern United States, combined to increase the number of people who identified as American Indian/Alaska Native. The sample included 147 people (M age = 28.5 years; SD = 16.26), of which 57 percent are female. The surveys collected data on adversities (polyvictimization, other adversities, county poverty), psychosocial strengths (psychological endurance, sense of purpose, religious meaning making, compassion, and community support), and P-HRQOL. The full model accounted for 24 percent of the variance in P-HRQOL, with strengths explaining more than twice as much variance as adversities (13 percent versus 6 percent). A sense of purpose showed the most promise for supporting P-HRQOL. Regarding implications, authors recommend exploring a wider range of protective factors that might improve resilience in Native communities. Several evidence-based pathways to meaning making, such as narrative and mindfulness, may improve health outcomes for Native people.