Soft tissue sarcomas in neonates are rare and heterogeneous tumors. We report an aggressive neonatal undifferentiated round cell sarcoma with a YWHAE:NUTM2B fusion. The tumor was identified antenatally and the neonate underwent surgical resection at four days of age. Whole-genome and transcriptome sequencing of tumour and germline was undertaken to provide molecular characterization and elucidate possible novel therapies. In addition to molecular characterization of a YWHAE:NUTM2B fusion, RNA expression outliers were described. Targeted therapy was not pursued due to rapid clinical decline. Understanding the genomic profile of rare tumors remains important in the development of novel therapeutic strategies.