Soft tissue sarcomas (STSs) are rare, making up less than 1% of all cancers, with uterine sarcomas accounting for 4–9% of uterine malignancies. The most common type is uterine leiomyosarcoma (uLMS), an aggressive cancer that develops from the smooth muscle of the uterus. The primary treatment for uLMS is surgical resection, usually through total abdominal hysterectomy and bilateral adnexectomy. Adjuvant chemotherapy has not shown consistent benefits in early-stage cases, but it is commonly used for advanced or recurrent cases with unresectable lesions. Doxorubicin (Dox) is the standard first-line chemotherapy, though combining it with trabectedin has shown better survival rates in clinical trials. Genetic studies have identified mutations in uLMS, including TP53, RB1, and BRCA2. New treatments, such as poly adenosine diphosphate-ribose polymerase (PARP) inhibitors for HRD (homologous recombination deficiency)-positive cases, are being explored. Since uLMS is characterized by chromosomal instability, future therapies may need to be tailored based on genetic and chromosomal alterations. Due to its rarity, innovative strategies, such as large-scale registry studies and genomic data collection, are needed to evaluate treatment effectiveness and develop better therapies.