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Introduction: While survival rates among children with cancer are high, a significant proportion of the solid tumors are considered as hard to treat (HTT). Next generation sequencing (NGS) offers the ability to detect molecular changes in tumors. Its implementation may allow usage of targeted therapy for tumors that fail to respond to acceptable oncological treatment. Furthermore, these therapies are characterized by milder side effects than chemotherapy. NGS may also aid in establishing pathological diagnoses and occasionally, identifying cancer-predisposition syndromes. However, the benefit of NGS in the pediatric population is not clear., Aims: Evaluating the benefit of NGS in children with 'HTT' Tumors., Methods: A retrospective study of the usage of NGS in pediatric 'HTT' in the Department of Pediatric Hemato-Oncology at the Hadassah Medical Center. Patients' demographic and clinical characteristics, molecular changes in tumor, their influence on medical decisions and disease course - were all documented., Results: Forty-seven NGS tests from 'HTT' tumors were completed between January 2018 to August 2020. The results of these tests dictated medical decisions in 18 cases (38.3%) while it proved utility in 10 cases (21.3%). Clinical response to targeted therapy, clarification of diagnosis and identification of germline changes were documented in 3 (6.4%), 4 (8.5%) and 3 (6.4%) cases, respectively., Conclusions: The usage of NGS may benefit children with 'HTT' and tumors with difficult diagnoses and in some cases may be life-saving., Discussion: Cost-benefit considerations presumably prevent the assimilation of NGS tests in the standard care of pediatric oncology. It is possible that the current results will strengthen the more accurate usage of theses genomic techniques in children with 'HTT'.