Non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) is a group of over 70 tumors that occur across the age range and account for approximately 4 % of childhood cancers. Patients with metastatic or relapsed NRSTS have a dismal prognosis. The histologic, molecular, and clinical heterogeneity of NRSTS and the rarity of individual types pose unique challenges to the study of these diseases. The Children's Oncology Group (COG) Soft Tissue Sarcoma (STS) Committee established a NRSTS Novel Agents Working Group to identify and prioritize agents for further study in pediatric NRSTS, similar to recent efforts in Ewing sarcoma, rhabdomyosarcoma and osteosarcoma. We report the framework that was used to evaluate agents and the results of this evaluation. Immune checkpoint inhibitors and tyrosine kinase inhibitors were identified by the COG STS Committee as candidate classes of agents for inclusion in phase 2 or phase 3 clinical trials of pediatric NRSTS. Gaps in the existing literature and practical barriers were identified for additional classes of agents to guide future drug development efforts.