Background: No previous studies have examined the relationship between stress, anxiety, and depression among pharmacists in Vietnam. Objectives: This study aims to investigate the correlation between stress, anxiety, depression, and job satisfaction among hospital pharmacists in Vietnam. Methods: The study comprised a 12-month cross-sectional survey in Can Tho City, Vietnam, with 11 conveniently selected hospitals. Out of 305 the distributed questionnaires, 303 were completed (99.3% response rate). The 21-item depression, anxiety, and stress scale (DASS-21) assessed stress, anxiety, and depression (21 items), while job satisfaction was measured using a 44-item questionnaire. Results: The study revealed a prevalence of 15.5% for stress, 27.1% for anxiety, and 20.5% for depression among hospital staff. Additionally, the majority of hospital staff (72.9%) reported being satisfied with their job. Those with more than 2 children (95% CI = 1.183-14.519) were nearly 4 times as likely to experience higher stress. Female respondents (95% CI = 1.34-5.92) and those who rented (95% CI = 1.05-3.55) were more likely to encounter anxiety. Those living outside Can Tho City (95% CI = 1.32-9.88) were at a 3.61 times higher risk of depression, while individuals who had been working at the hospital for 5 to 10 years (95% CI = 0.17-0.82) had a lower risk of depression. Increased depression (aOR = 0.441; 95% CI = 0.21-0.94) was linked to job dissatisfaction. Conclusion: Depression was significantly associated with job dissatisfaction. The study findings suggest that management agencies should implement prevention and intervention strategies to reduce mental health issues among hospital pharmacists.