Neuroblastoma is a type of cancer that affects the sympathetic nervous system and is the most common extracranial solid tumor in children. Difluoromethylornithine (DFMO) is a drug that has shown promise as a treatment option for high-risk neuroblastoma. This review aims to provide an overview of the current research on the use of DFMO in neuroblastoma treatment. The review includes a discussion of the mechanisms of action of DFMO, as well as its potential for use in combination with other treatments such as chemotherapy and immunotherapy. The review also examines the current clinical trials involving DFMO in high-risk neuroblastoma patients and provides insights into the challenges and future directions for the use of DFMO in neuroblastoma treatment. Overall, the review highlights the potential of DFMO as a promising therapy for neuroblastoma and highlights the need for further research to fully understand its potential benefits and limitations.