Objective: The purpose of the research was to explore nurses' professional well-being at work and its differentiating factors. Methods: The tool of the cross-sectional, quantitative, descriptive research was a questionnaire, which included questions referring to sociodemographic characteristics, along with validated questionnaires widely used in the international research literature (Maslach Burnout Inventory (hereafter MBI), Beck Depression, Diener Quality of Life) and questions focusing on the exploration of the workplace climate. Following a simple, non-random sampling procedure, the responses of 581 professionals working in nursing job positions were included in the analysis. Results: Examining burnout, it has been found that the nurses involved in the survey show a more unfavourable picture in the dimensions of depersonalization and emotional exhaustion, compared to MBI normal values. On the other hand, the average value of personal accomplishment proved to be higher among them, which means that the respondents feel their efforts to be more successful and more positive at work. The organizational characteristics of the workplace (F = 2.875; p = 0.009), along with the social appreciation of the job position (F = 4.275; p < 0.001) significantly influence overall satisfaction with life. Conclusions: The promotion of well-being at work is of utmost importance among health professionals (who are increasingly exposed to stress and burnout), especially among nurses directly participating in inpatient care.