Aim: This study aimed to determine the work-related stress and job satisfaction levels of nurses working in a university hospital and to examine the factors influencing these variables. Method: The study employed a descriptive and correlational research design. The sample consisted of 371 nurses. Data were collected between January 1 and March 31, 2022, using a Personal Information Form, the Minnesota Job Satisfaction Scale, and the Nurse Stress Scale. Results: The findings indicated that the unit of employment (intensive care, emergency services, and operating room), marital status (being single), and the external satisfaction subdimension were predictors of work-related stress. These variables explained 13.2% of the variance in work-related stress (Adjusted R2 = 0.132). The unit of employment (intensive care, emergency services, and operating room), the suffering patient subdimension, the workload subdimension, and number of children (having one child) were identified as predictors of job satisfaction. These variables explained 14.5% of the variance in job satisfaction (Adjusted R2 = 0.145). Conclusion: Nurses' work-related stress and job satisfaction levels were found to be moderate. Given the importance of these factors for the quality of nursing care, it is essential to identify nurse groups at higher risk for work-related stress and low job satisfaction and prioritize them for intervention. Continuous monitoring of stress and job satisfaction levels, workload planning, and appropriate interventions should be implemented to reduce stress and enhance job satisfaction.