Backgrounds <p>The mental health and wellbeing of university students have become increasingly pressing concerns, with rates of psychological distress rising in recent years. This study investigates the factors contributing to psychological distress among university students, focusing on resilience, coping self-efficacy, acculturation, and cultural backgrounds.</p> Methods <p>Utilizing a biopsychosocial model, the study examines how sociocultural stressors and individual coping mechanisms interact to influence mental health outcomes. Data were collected from 291 undergraduate domestic and international psychology students at a large urban university in the United States during the Spring 2023 semester.</p> Results <p>Results indicated that domestic students reported significantly higher levels of psychological distress and life stressors compared to international students. Factors such as stressful life events, resilience, and coping self-efficacy were significantly associated with psychological distress. Acculturation was not directly associated with distress but was linked to coping self-efficacy among international students. Regression analysis revealed that higher numbers of stressful life events, lower resilience, and domestic residence are associated with psychological distress.</p> Conclusions <p>The study highlights the importance of protective factors like resilience and coping self-efficacy in managing life stress and adversity among university students. These insights can inform efforts to promote mental health and wellbeing through resilience-building, coping strategy workshops, and community engagement.</p>