Soft tissue sarcomas (STSs) are a diverse group of malignant tumors that originate in the connective tissues, including lymphatics, vessels, smooth and striated muscles, fat, fascia, synovium, endothelium, and reticuloendothelium. These tumors are found to be more prevalent in males as compared to females. Among STS, rhabdomyosarcoma (RMS), which is committed to skeletal muscle lineage, is the third most common pediatric extracranial neoplasm after neuroblastoma and Wilms’ tumor, comprising 15% of all solid tumors. The remaining cases comprise a diverse group of non-rhabdomyosarcomas (NRSTS), including synovial sarcoma, fibrosarcoma, and malignant peripheral nerve sheath tumors, among others. RMS exhibits a bimodal incidence pattern, with nearly two-thirds of cases diagnosed in children under 6 years of age, followed by a second peak in mid-adolescence. RMS can arise in various anatomical regions, with 35% occurring in head and neck, 22% in the genitourinary followed by trunk (27%) and extremities (14%) (Table 62.1). For localized rhabdomyosarcoma, the five-year overall survival rate reaches around 70% with local control being achieved in 80–90% of these cases.