Background: Nurses face a significant burden of occupational stress, which can have detrimental effects on their physical and mental health. This is exacerbated by factors such as long working hours, heavy workloads, patient acuity, and exposure to traumatic events. Objectives: The present study aimed to investigate the mediating role of job satisfaction in the relationship between occupational stress and life satisfaction among nurses. Methods: This investigation employed a correlational design utilizing structural equation modeling (SEM) to examine the relationships between variables. A convenience sample of 182 nurses completed self-report questionnaires assessing life satisfaction, job satisfaction, and occupational stress. The collected data were subsequently analyzed using SEM techniques with SPSS-25 and AMOS-24 software. Results: A significant and negative relationship was found between occupational stress and job satisfaction (β = -0.47, P < 0.001). The relationship between job satisfaction and life satisfaction was also positive and significant (β = 0.40, P < 0.001). The results indicated that the relationship between occupational stress and life satisfaction was not significant (β = -0.08, P = 0.311). Additionally, job satisfaction mediated the relationship between occupational stress and life satisfaction (P < 0.001). The model fit indices were satisfactory, indicating a good fit to the data: IFI = 0.95, CFI = 0.99, NFI = 0.98, GFI = 0.99, and RMSEA = 0.06. Conclusions: The findings of this study underscore the importance of creating supportive work environments for nurses. Job satisfaction plays a critical role in mitigating the negative effects of occupational stress, highlighting the need for organizations to implement effective stress management programs, promote work-life balance, encourage open communication, and invest in professional development.