Background In light of the COVID-19 pandemic, the distribution of social support for mental health problems has likely become unequal. Family- and community-based social support has been recognized as a promising approach for mental disorders; however, limited global frameworks have been applied to developing countries such as Vietnam. Objective The aim of this study was to evaluate the quality of life and social support among patients with mental health disorders in Vietnam and to investigate the factors associated with quality of life among these patients. Methods A cross-sectional study was conducted on 222 psychiatric patients in Hanoi from 2020 to 2022. A structured questionnaire was developed based on four standardized scales: Mental Well-Being-5 scale, Multidimensional Scale of Perceived Social Support, EuroQoL-visual analog scale (EQ-VAS), and EuroQoL-5 dimensions-5 levels (EQ-5D-5L) scale. Tobit regression was used to identify factors associated with the EQ-5D-5L and EQ-VAS scores. Structural equation modeling was applied to verify the relationship between quality of life and social support. Results The results showed that perceived support from family scored the highest compared to support from friends and significant others. Patients with depression reported the lowest quality of life and perceived social support. Structural equation modeling showed a root mean square error of approximation of 0.055 (90% CI 0.006-0.090), comparative fit index of 0.954, Tucker-Lewis index of 0.892, and standardized root mean squared error of 0.036 (P<.001). The hypothetical model indicated statistically significant correlations between EQ-VAS score and social support (P=.004), EQ-5D-5L and mental well-being (P<.001), and social support and mental well-being (P<.001). Critical deterioration of quality of life and inconsistency in social support for patients with mental illness were also recorded. Conclusions There is a need to enhance social support and service delivery in Vietnam, focusing on occupation and quality of life. The correlations between social support, quality of life, and mental health issues suggest the potential of a clinical-social integrated intervention model of care.