Background: Stress at work is a significant occupational risk that diminishes performance and job satisfaction. Objectives: This study aimed to assess the relationship between job satisfaction and various factors of the job demand-control-support (JDCS) model among 840 nurses working in public hospitals affiliated with Mazandaran University of Medical Sciences, Iran. Methods: The Job Content Questionnaire and the Minnesota Satisfaction Questionnaire were utilized to assess various aspects of the JDCS model and job satisfaction, respectively. The structural equation model (SEM) was employed to explore the relationships between variables. A significance level of P < 0.05 was considered. Results: The findings revealed that the highest average scores were for skill discretion (30.92 ± 10.34) and decision authority (30.82 ± 6.91), while the lowest mean scores were related to social support (21.37 ± 7.60) and job insecurity (7.78 ± 1.49), indicating high levels of job stress among participants. The study identified direct and positive relationships between demand and control (r = 0.58, P = 0.021), control and support (r = 0.51, P = 0.032), and demand and support (r = 0.87, P = 0.009). Social support had a positive influence on job satisfaction (standardized = 0.75, P = 0.008) and a negative effect on job insecurity (standardized = -0.56, P = 0.009). Control negatively impacted job insecurity (standardized = -0.1, P = 0.02) and positively affected job satisfaction (standardized = 0.012, P = 0.012). Additionally, "job insecurity" moderated the effect of "control" on "job satisfaction" (standardized = 0.02, P = 0.005). Conclusions: Higher job demands and control contribute to increased dissatisfaction and insecurity among nurses. Conversely, nurses who receive more social support feel more secure and satisfied. To enhance job satisfaction and reduce insecurity, efforts should focus on increasing support and managing control and demand, as these factors significantly influence job performance and satisfaction.