Purpose: Using an identical experimental structure with both Thai and Singaporean undergraduates, we investigated relationships (interactions) among social support, stress, resilience, mindfulness, and self-efficacy on psychological well-being (PWB). Stress indicated a negative influence on PWB, but mindfulness, resilience, self-efficacy, and social support indicated positive influences. Methods: A cross-sectional predictive design was used with 966 Thai and 673 Singaporean university students. After calculating an adequate sample size and performing convenience sampling, we administered the following six standard scales: the Perceived Stress Scale, the Connor–Davidson Resilience Scale, the Mindfulness Awareness Scale, the General Self-Efficacy Scale, the Multi-dimensional Scale of Perceived Social Support, and the Psychological Well-being Scale—along with a demographic questionnaire. Descriptive statistics, correlation analysis, and structural equation modeling were performed for participants’ PWB. Results: Mindfulness had significant effects for both factors of PWB, including autonomy and growth, and cognitive triad, across two samples. In the Thai sample, resilience most strongly predicted autonomy and growth and perceived stress did so the cognitive triad, whereas in the Singaporean sample, perceived control most strongly predicted autonomy and growth and support from friends did so the cognitive triad. Conclusion: These findings provide specific knowledge toward enhancing psychosocial interventions and toward promoting PWB to strengthen mindfulness, resilience, perceived control of stress, and social support. stress, resilience, mindfulness, psychological well-being, university students