Due to their difficult profession, nurses often experience stress, anxiety, and sadness. High-stress units like the ICU and ER are especially stressful, although medium and low-stress departments such as Outpatient, and general hospital in patient wards may have their own pressures. This study compared nurses' stress, anxiety, and depression in high, medium, and low-stress hospital units in King Fahad Medical City. The study used the Depression, Anxiety, and Stress Scale (DASS-21) to measure psychological distress and a demographic and workplace questionnaire to measure workload, shift patterns, and sleep duration. SPSS was used for descriptive and inferential statistics like chi-square testing and regression analysis. Key findings showed that high-stress nurses reported significantly higher depression and stress than low-stress nurses. Interestingly, medium-stress departments had higher anxiety levels, defying stress preconceptions. Nationality and shift patterns affected mental health outcomes, with non-Saudi nurses and those working rotating shifts suffering more stress and anxiety. Mental health programs customized to each hospital unit's pressures are needed, according to the report. Workload management, stress-reduction, and sleep hygiene can reduce the psychological burden of nursing, especially in high-stress conditions.