The responsibilities of nurse managers are complex. Their actions are crucial to providing the best possible care to patients and to the success of health care organizations. Thus, nurse managers’ work engagement is essential. However, understanding of the antecedents of nurse managers’ work engagement is lacking. The job demands–resources theory posits that work engagement is contingent upon job resources and demands. Therefore, the aim of this study was to explore which job demands and resources exert a major influence on nurse managers’ work engagement. Considering the literature, job resources and demands potentially relevant to nurse managers’ work engagement were identified. To investigate the associations between these potential antecedents and nurse managers’ work engagement, the study employed a cross-sectional survey. The dataset for analyses comprised 408 nurse managers in Germany and was analyzed by multiple linear regression. The study variables accounted for 26% of the variance in nurse managers’ work engagement. Positive associations were detected between the job resource of empowering leadership and nurse managers’ work engagement. Regarding job demands, lack of formal rewards and work–life interferences had negative effects on work engagement. The findings suggest that the job demands–resources theory can explain nurse managers’ work engagement. However, not all job resources and demands considered were determined to be influential. In conclusion, empowering leadership should be promoted in the work environment of nurse managers. Nurse managers should be provided engaging financial and nonfinancial rewards. Work–life interferences should be systematically mitigated.