Undifferentiated uterine sarcomas (UUS) are malignant mesenchymal tumours without clear differentiation patterns, commonly diagnosed by ruling out other conditions. Next-generation sequencing (NGS) sequencing has identified two subtypes within UUS: simple genomic sarcomas, which have near-diploid karyotypes and identifiable alterations, and complex genomic sarcomas characterised by chromosomal instability. Complex genomic UUS present high mitotic activity and lymphovascular invasion, and often test positive for p53 and p16. Diagnosis often occurs at advanced stages, and they have a poor prognosis, with a 5-year survival rate between 10% and 30%. Surgical management, typically a complete hysterectomy, remains the primary treatment. However, the role of adjuvant chemotherapy and radiotherapy is unclear. In metastatic cases, single-agent doxorubicin is a standard treatment, with alternative options like trabectedin, gemcitabine, and pazopanib in advanced lines of treatment. Simple genomic sarcomas present with well-identified oncogenic drivers, such as NTRK fusion, or tumour suppressor gene losses such as SMARCA4 deficiency and DICER1 mutation. Uterine sarcomas with NTRK fusion are typically found in younger women and may exhibit aggressive behaviour. Targeted therapies, such as TRK inhibitors (larotrectinib and entrectinib), have shown partial or complete tumour responses in a small number of cases reported in the literature. SMARCA4-deficient undifferentiated uterine sarcoma is another rare but aggressive subtype, with a median survival of 7–9 months. These tumours often show rhabdoid morphology and SMARCA4 loss, and emerging therapies like CDK4/6 inhibitors and immune checkpoint inhibitors are being explored for treatment. Uterine embryonal rhabdomyosarcomas with DICER1 mutations are typically present in young women around 30 to 40 years. They require multimodal treatment strategies, including chemotherapy and surgery, with conservative surgical management preferred when possible. A particular form called botryoid variant arises from the uterine cervix, presenting typically like a polyp, and has a better prognosis. Half of DICER1 mutations in rhabdomyosarcomas are germline alterations. DICER1 familial predisposition syndrome is especially associated with pleuropulmonary blastoma and ovarian sex cord stromal tumour.