Objective: This study aimed to identify factors related to anxiety and psychological well-being in college students, including occupational therapy (OT) majors, and to explore the associations between ego-resiliency and psychological well-being across major groups. Methods: A total of 200 college students in B Metropolitan City participated in this study, including 80 OT majors and 120 non-OT majors. Ego-resiliency, psychological well-being, and anxiety were measured. The collected data were analyzed using SPSS 29.0 through frequency analysis, Welch’s t-test, logistic regression, and subgroup simple regression analysis. Results: Four-year college students showed significantly higher state anxiety than 3-year college students and were approximately 2.26 times more likely to belong to the high-risk anxiety group. No significant mean differences were found between OT and non-OT majors in the major psychological variables. However, in the subgroup analysis, ego-resiliency showed a significant positive association with psychological well-being in the OT major group, whereas this association was not statistically significant in the non-OT group. Conclusion: State anxiety showed differences related to the school system, and ego-resiliency was significantly associated with psychological well-being in the OT major group. These findings suggest the need for educational support that considers the academic environment to reduce anxiety, along with interventions to strengthen ego-resiliency among OT students.