Cancer is considered one of the dominant life-threatening diseases in children. Working in the field of pediatric oncology, although rewarding, can be a source of stress and emotional burden for health care providers. The aim of this systematic review was to summarise the evidence regarding the occupational stress of health care providers working with pediatric cancer patients. Extensive search of the Pubmed and Scopus databases was performed to identify studies relevant to the topic. Initial search retrieved 657 studies. The reviewing investigators, after applying the inclusion/exclusion criteria, extracted data to critically appraise the quality of evidence. The final step of search concluded in 23 studies of heterogeneous design. Results revealed two main domains of which occupational stress derived from i) the interaction of the health care provider with the patient and the family, and ii) several organisational factors, such as hierarchical structures, experience, workload, and low organisational support. Literature on the stress of pediatric oncology staff is limited. The rather small sample sizes of the studies, the heterogeneity of methodological design, the lack of assessment from a sociological point of view, as well as the limited psychometric instruments adapted to pediatric oncology staff, make the validity of the results questionable. Further research is warranted to obtain a more accurate view of the field, to identify a cause-effect relation between work-related stress and pediatric oncology staff, and, more importantly, to guide future recommendations on support systems and stress management training within pediatric oncology settings.