Objective To explore the intrinsic mechanism of the relationships among perceived organizational support, resilience, decision fatigue, and job performance of clinical nurses, and to provide a basis for managers to improve organizational dynamics and implement precise human resource management.Methods A survey was conducted among 925 clinical nurses from a tertiary hospital using the general information questionnaire, the Nurses′ Perceived Organizational Support (NPOS), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), the Decision Fatigue Scale (DFS) and the Job Performance Scale(JPS). Hierarchical regression and Bootstrap methods were used for mediating effect analysis. Results The total scores of NPOS, CD-RISC-10, DFS and JPS were (47.87±9.75), (24.79±7.06), (10.19±5.91), and (98.25±12.31) points, respectively. Job performance was positively correlated with perceived organizational support and psychological resilience, and negatively correlated with decision fatigue (all P<0.05). Perceived organizational support directly influenced job performance, while psychological resilience and decision fatigue played a chain mediating role between perceived organizational support and job performance, accounting for 4.85% of the total effect. Conclusion Clinical nurses′ job performance is at a relatively good level. Perceived organizational support can influence job performance through the mediating pathways of resilience and decision fatigue. Managers should enhance organizational support (e.g., providing emotional recognition and decision-making aids), implement psychological resilience training programs, and streamline decision-making processes to optimize job performance.