Background: Occupational burnout is intricately linked to a spectrum of physical disorders encompassing respiratory, cardiovascular, and gastrointestinal conditions, as well as manifestations such as headaches, type 2 diabetes, elevated cholesterol levels, chronic fatigue, and muscle pain. Despite this association, there remains a paucity of research on the specific risk factors contributing to burnout among nurses in China. Methods: This cross-sectional study utilized convenience sampling to recruit participants, with data analyzed from 1,774 nurse staffs. Psychosocial traits were assessed using the Three-Item Loneliness Scale for loneliness, the Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety symptoms, the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms, the Connor Davidson Resilience Scale–10 item (CDRISC-10) for resilience, and the Maslach Burnout Inventory-Human Service Survey (MBI-HSS) for burn out. Restrictive cubic spline analysis to investigate the dose-response relationship between years of experience and burn out. Multivariate linear regression was employed to investigate the relationship between burnout and various risk factors. Results: After controlling for basic demographic variables, good sleep quality was associated with a reduction in emotional exhaustion (β = −0.307, p < 0.001), while loneliness (β = 1.334, p < 0.001), depressive symptoms (β = 0.896, p < 0.001), and anxiety symptoms (β = 0.504, p < 0.001) were significantly associated with increased emotional exhaustion. Moreover, higher levels of resilience were positively associated with personal accomplishment (β = 0.635, p < 0.001). Regarding depersonalization, loneliness (β = 0.577, p < 0.001), depressive symptoms (β = 0.429, p < 0.001), and anxiety symptoms (β = 0.152, p < 0.01) were found to increase its level. Conversely, good resilience was associated with a decrease in depersonalization (β = −0.069, p < 0.001). The non-liner association between year of experience and emotional exhaustion was significantly (p < 0.05). Conclusion: Our findings revealed that significant risk factors contributing to burnout among nursing staff including bad sleep quality, loneliness, lower level of resilience, anxiety symptoms, depressive symptoms. Moreover, a nonlinear correlation between years of experience and the likelihood of experiencing emotional exhaustion was exist.