Job satisfaction of staff nurses carries significant organizational consequences, such as staff well being, commitment, retention and the quality of healthcare services provided as all of these are closely related. The present study aimed to find out the factors influencing job satisfaction of staff nurses in hospitals in Kozhikode District. The study employs a quantitative descriptive analysis approach method cross-sectionally, which explores the effect of workload, staffing conditions, leadership, supervisory support, professional empowerment and autonomy, organizational support, and occupational stress and job burnout on job satisfaction. The analysis is conducted using a synthetic data set that consists of 220 synthetic observations that have been built for demonstration of the analytical model. The proposed relationships examined using descriptive statistics, reliability analysis, Pearson correlation analysis, group comparison tests and multiple regression analysis. The scale items were internally consistent, with Cronbach's alpha coefficient items between 0.842 and 0.914. The regression model explained 62.7% of the variance in job satisfaction. Job satisfaction was significantly positively associated with workload, levels of staffing, leadership and supervisory support, organizational support, and job empowerment and autonomy. The second strong factor and only statistically significant negative predictor was occupational stress and occupational burnout. The results showed that job satisfaction of staff nurses is a product of the complex interplay of workplace demands and organizational resources. The study underscores, among others, the significance of manageable workloads, supportive leadership, institutional support, professional autonomy and effective strategies to lower occupational stress and burnout. Because the analysis is synthetic data, the results obtained are considered as analytical and methodological indications rather than real survey of the job satisfaction level of staff nurses from Kozhikode District.