In recent years, immunodeficiency condition has experienced a rise among children, who are at risk of invasive fungal infections (IFI) due to their health condition. Cancer, non-malignant hematological diseases, as primary immunodeficiencies, hematopoietic stem cell transplantation (HSCT), extreme prematurity, or critically ill condition in Pediatric Intensive Care Unit (PICU) are some immunosuppressive situations in children. The use of oncologic therapies, including immunotherapy and monoclonal antibodies, for the treatment of the aforementioned health conditions has led to an increase in morbidity and mortality rates of IFI in children. The underlying diseases and their management, comorbidities, the diagnostic tests used (both molecular and imaging), as well as the treatment used can be significantly different between adult patients and children admitted to PICU or with cancer. In pediatrics, the treatment of IFI is based primarily on pharmacokinetic studies performed in adults. In higher risk patients prophylaxis should be considered and, in the case of an IFI diagnosis, an antifungal treatment should be administered as early as possible, supported by the reversion of the immune dysfunction and surgery when appropriate.