Background: Pediatric cancer is a global problem, and some studies have highlighted that nurses caring for these children experience work-related challenges, which makes many children with cancer to be left with terminal diagnoses, unnecessary suffering; and also, job dissatisfaction among the nurses. But no study has explored this phenomenon among pediatric oncology nurses in Ghana. This study aims to explore and understand the challenges that the pediatric oncology nurses experience when caring for children with cancer in Ghana.Methods: An exploratory qualitative research design study was conducted from August 2019 - April 2020. The study was conducted at the Pediatric oncology unit which is located at the Tamale Teaching Hospital (TTH), Ghana. The study was conducted among 14 Ghanaian pediatric oncology nurses who were purposively sampled. The data collection instrument was a face-to-face in-depth semi-structured interview. The interviews were recorded, transcribed verbatim, and analyzed inductively using Elo and Kyngas content analysis approach. The criteria proposed by Guba and Lincoln were used to ensure the validity of the study.Results: The results showed that the challenges that the pediatric oncology nurses experience includes: Time-consuming care, Low Job motivations, Inadequate logistics, Work stress, Reduced labor force, Low knowledge level, Absence of teamwork and the Perception of contracting cancer. Conclusions: The results point to several organizational and personal constraints experienced by the nurses who work at the pediatric oncology ward. There is the need for the administrative managers of hospitals, government and other stakeholders to invest in human, material and financial resources for delivering childhood cancer care services. It is hoped that by addressing these challenges, it would lead to further improvement in the care that is provided to children with cancer.