Abstract: Objective To explore the mechanisms and configurational paths of factors influencing job burnout of medical staff in order to propose preventing and alleviating measures against such conditions. Methods A total of 64 medical staff from public hospitals of various levels in a district of Tianjin were surveyed with questionnaires of the Occupational Risk Perception Scale and the Maslach Burnout Inventory (MBI). Fuzzy set qualitative comparative analysis (fsQCA) was utilized to identify the core influencing factors and configurational paths leading to job burnout. Results The mean of the total score of job burnout among 64 medical staff was (33.06 ± 13.41) points, with an average item score of (2.2 ± 0.89) points. The prevalence of job burnout was 60.94% (n = 39). Five configurational paths leading to job burnout were identified. The consistency of these five paths exceeded the threshold of 0.8 (range: 0.849 to 0.974), with an overall solution consistency of 0.896 and an overall coverage of 0.582. Configurations 1 to 4 formed the “physical sensation-induced” burnout paths, identifying “workload” and “occupational injury risk” as core conditions and risk factors such as personal development, social relations, or organizational management as supplementary factors. Configuration 5 formed the “psychological incentive-induced” path, which demonstrated that burnout was triggered by 3 core conditions of high personal development risk, high economic risk, and high occupational injury risk, even when workload, organizational management, and social relation risk were relatively low. Conclusions Job burnout of medical staff emerged from the specific interplay of multiple risks across various contexts. Interventions should target both physical sensation factors and psychological incentive factors by reducing workload, preventing occupational injuries, and addressing personal development and economic income issues in order to lower the risk of job burnout among medical staff.