Background <p>While the relationship between perceived stress and job satisfaction is well-established, the underlying mechanisms, particularly the roles of job burnout and psychological capital, have not been thoroughly examined in nurse managers.</p> Objective <p>This study aims to examine how job burnout (emotional exhaustion, depersonalization, and personal accomplishment) mediates the relationship between perceived stress and job satisfaction, and to assess the moderating role of psychological capital in these pathways.</p> Methods <p>A cross-sectional study was conducted with nurse managers from 20 hospitals in Henan Province, China. Participants completed validated questionnaires, including the Perceived Stress Scale, Maslach Burnout Inventory, Psychological Capital Questionnaire, and Minnesota Satisfaction Questionnaire. Moderated mediation analyses were performed using SPSS PROCESS Model 59 to explore the hypothesized relationships.</p> Results <p>A total of 784 nurse managers participated. The mean job satisfaction score was 78.06 (SD 12.03). All three dimensions of job burnout significantly mediated the association between perceived stress and job satisfaction. Psychological capital moderated both the direct and indirect effects in the pathways “perceived stress → emotional exhaustion → job satisfaction” and “perceived stress → depersonalization → job satisfaction,” as well as the second stage of the “perceived stress → personal accomplishment → job satisfaction” pathway.</p> Conclusion <p>These findings suggest that job burnout is a critical mediator in the relationship between perceived stress and job satisfaction, with psychological capital serving as an important moderator. Enhancing psychological capital may help reduce the negative impact of stress and burnout on job satisfaction, offering valuable insights for improving healthcare management practices.</p> Clinical trial number <p>Not applicable.</p>