Aims: Burnout syndrome is a phenomenon that is becoming ever more widespread, especially in workers such as nurses who have heavy workloads and time pressures. The progression of burnout syndrome has been shown to be related to both individual and work-related variables. The objective of this study is to examine the risk and protective roles played by work-related and personal variables, both sociodemographic and psychological, in the development of burnout in nurses. Method: The sample was composed of 1236 nurses aged between 21 and 57 years, with a mean age of 31.50 years (SD = 6.18). Women accounted for 84.5% (n = 1044), and the remaining 15.5% (n = 192) were men. Exploratory tests were performed to understand the relationships between burnout and other variables, and a binary logistic regression was conducted to understand the roles of these variables in the incidence of this syndrome. Lastly, a regression tree was constructed. Results: The results show that the sociodemographic variables examined are not related to the level of burnout in nurses. However, certain work-related variables, such as spending more time with colleagues and patients and reporting good-quality relationships, exhibit a negative relationship with the occurrence of burnout. Of the psychological variables, the stress factors conflict-social acceptance and irritability-tension-fatigue, as well as informative communication, are shown to be risk factors for the appearance of burnout in nurses. In contrast, the communication skills factor, empathy, and energy-joy exert a protective function. Conclusion: Identifying the variables that influence the occurrence of burnout syndrome and understanding the manner in which they exert their influence are key elements in the development of effective prevention and intervention of burnout in nursing.