Background: Nursing staff retention is an ongoing concern within pediatric hematology/oncology settings globally. Work-related stressors cause emotional burden, psychological distress, and burnout to which nurses respond by leaving their workplace. Consequently, workplace culture and functionality are negatively impacted, quality of care reduces, and potential harm to patients increases. This paper aims to identify the “most” influencing factors for intention to leave among pediatric hematology/oncology nurses. Methods: A systematic search was undertaken on 29 July 2021 across five electronic databases, Cumulative Index to Nursing and Allied Health Literature, Joanna Briggs Institute, MEDLINE, PubMed, and Web of Science, using MeSH and keywords related to pediatric hematology/oncology nurse retention. Results: The initial search yielded 283 articles. Following abstract and full-text review, nine articles met inclusion criteria. Across all studies, strong links between health service organizational factors (e.g., unit acuity and time constraints), clinician demographics (e.g., age, education, experience, and coping mechanisms), and nursing retention within pediatric hematology/oncology settings were observed. Direct patient care and long-term relationships with pediatric hematology/oncology patients were identified as the most frequent and intense stressors, while also presenting the most rewarding aspect of the nurse's work. Discussion: Clinician burnout and retention were found to be complex and multifaceted organizational and individual issues, which most importantly evolved from accumulative exposure to specialty-specific stressors. Interventions to prevent clinician burnout and improve staff retention, therefore, need to comprise individual and organizational level strategies specific to the healthcare context.