Objective: To examine the relations of science, technology, engineering, and mathematics's (STEM) self-efficacy, outcome expectations, interests, and contextual supports and barriers to STEM educational goals in college students with disabilities from racial and ethnic minority backgrounds. Design: Quantitative descriptive research design using hierarchical regression analysis (HRA). Participants: 115 underrepresented minority students with disabilities receiving services from the National Science Foundation (NSF) funded Minority-Disability (MIND) Alliance in STEM project at Hunter College, City University of New York and Southern University at Baton Rouge for the years 2008-2011. Outcome Measures: The Social-Cognitive STEM measures. Results: The HRA results indicated that gender, advanced placement (AP) classes, father's educational level, academic milestone self-efficacy, and STEM interest were significant predictors of goal persistence in African American and Hispanic college students with disabilities. The final model accounted for 57% of the variance in STEM persistence, which is considered a large effect size. Conclusion: The research findings provide good support for the use of the social cognitive career theory (SCCT) framework to identify predictors of STEM persistence and to design academic retention services and career development interventions for college students who are underrepresented minorities with disabilities.