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Housing insecurity and substance use disorder (SUD) are critical public health issues in the USA, with significant implications for health outcomes. This study evaluated the intersection of housing insecurity, SUD, and psychosis among Medicaid enrollees in an urban center in Oregon. Using data from Health Share of Oregon, we identified three distinct cohorts-individuals with housing insecurity, those with SUD/psychosis, and those with both conditions. Key outcomes included inpatient admission rates, average lengths of stay, and 30-day readmissions. The findings indicate that housing-insecure individuals with SUD/psychosis show greater acute care utilization than the other two cohorts. Inpatient admissions for housing-insecure individuals with SUD/psychosis were over twice as high as those without housing insecurity (29.7% vs. 12.4%), nearly three times as high as those without SUD/psychosis (29.7% vs. 9.5%), and almost ten times higher than those without either (29.7% vs. 3.0%). There were likewise corresponding increases in ambulatory-sensitive hospitalizations, 30-day readmissions, and longer hospital stays. Effective interventions should address both housing and healthcare needs, including comprehensive case management and improved access to physical, behavioral, and mental health services integrated with housing programs and services. These strategies could mitigate acute care utilization and improve overall health outcomes for these vulnerable populations.