The purpose of this study was to identify physical and psychosocial working conditions to improve well-being at work among healthcare staff. This is a potent area of inquiry given the relationship between healthcare staff well-being and service quality and other key organizational characteristics. However, while numerous studies in this area have used a quantitative methodology, very few have applied qualitative methodologies gathering subjective descriptions of the sources of well-being, providing in so doing significant data to explore in depth the factors that influence well-being in healthcare systems. We gathered qualitative data analyzing open-ended questions about risk and protective factors of well-being at work. The sample was made of 795 professionals answering an online questionnaire. Answers were coded and analyzed using the thematic analysis with an inductive approach (data-driven). We identified four themes strongly affecting professional well-being in health-care staff: , , , and . Our findings suggest possible strategies and actions that may be effective in helping to calibrate case-specific support and monitoring interventions to improve health and well-being of healthcare staff. We also discuss the implications of the study and suggest possible avenues for future empirical research.