First-line nurse managers have a pivotal role in the organization of health care but have to deal with significant job-related issues and problems in a changing and challenging health care environment. As their new roles are complex and often unclear, it might be expected that these professionals are at risk for occupational stress. The objective of this study is to analyze and describe relationships between job characteristics, and also interdisciplinary conflicts with physicians as potential predictors of occupational well-being (job satisfaction, psychosomatic distress, turnover intention, work engagement and burnout). this study had a cross-sectional design and used a web-based survey. This study was conducted in 2015 in 11 Belgian (Flemish) hospitals. All First-line nurse managers were eligible (N=481) and 318 respondents (66.1%) agreed to take part in the survey. A hierarchical regression analyses was applied to analyze relationships between predictors and outcomes. job demand and job control measures were predictive of all outcomes. Collaboration with doctors only predicted job satisfaction and turnover intention. Social support from management was predictive of turnover intention. Social support from colleague- first-line nurse managers was not predictive. Social support from the staff members (team) was however a strong predictor of all stress outcomes. Job demands, job control and social support of the team and management were all important predictors of occupational well-being in first-line nurse managers. All of these variables can be influenced by hospital management to improve the work conditions of this professional group in order to retain their workforce.