Background: Fever and neutropenia (FN) is a potentially life-threatening complication of chemotherapy in children with cancer. Aim: Our objectives were to describe the characteristics of episodes of FN experienced by our patients and evaluate their outcomes and factors affecting them. Material & Methods: A prospective observational study was conducted at Pediatric Oncology Department, South Egypt Cancer Institute, Assiut University. All pediatric patients ≤ 18 years with either hematological or solid tumors admitted with documented episodes of FN after receiving myelosuppressive chemotherapy were included in this study between February 2018 and February 2020.  Results: 200 episodes of FN experienced by 125 pediatric cancer patients were included. The median age was six years; 60% of the patients were boys. FN was more prevalent among patients with hematological malignancies. Associated comorbidities were reported in 10.5%. Eighty percent of episodes were stratified as high-risk, with profound neutropenia reported in 47%. The focus of infection was documented in 82% of episodes. Blood-stream infections were 53.1% for Gram-negative and 24.4% for fungal isolates. Infection-related mortality was reported in 7% of episodes. Diagnosis, disease status, risk stratification, presence of comorbidity, and the grade of neutropenia significantly affected the outcome. Conclusion: Although satisfactory therapeutic interventions for neutropenic patients with fever, life-threatening resistant bacterial and fungal isolates were reported at high rates that mandate calling for an urgent review of infection control policy.