Desmoid tumors are rare, locally infiltrating tumors that rarely metastasize. They often exhibit spontaneous regression in up to 20% of cases, but lack a standard treatment approach. Surgical resection is not favored due to high morbidity and recurrence rates. Systemic therapies have evolved, with tyrosine kinase inhibitors and gamma-secretase inhibitors (GSIs) showing significant clinical benefit. Nirogacestat, a GSI, has recently been approved and is a key treatment option. Other Wnt pathway inhibitors and newer drugs are under development. Cryoablation is also showing promise for extra-abdominal desmoid tumors. The Wnt pathway is central to desmoid tumor pathogenesis, with dysregulation leading to abnormal cell proliferation and fibrosis. The Notch signaling pathway also plays a critical role, and GSIs target substrates in this pathway. Nirogacestat has shown significant efficacy in clinical trials, with high progression-free survival and objective response rates. It causes ovarian dysfunction in some patients, but symptoms resolve upon discontinuation. Other GSIs like AL-101 and AL-102 are under investigation. Sorafenib and pazopanib are also used in treatment. Cryoablation is an attractive option for extra-abdominal desmoid tumors. Overall, systemic therapies like GSIs and tyrosine kinase inhibitors are now preferred for symptomatic patients, while watchful waiting is suitable for asymptomatic cases. The treatment landscape is evolving with new drugs and approaches.Desmoid tumors are rare, locally infiltrating tumors that rarely metastasize. They often exhibit spontaneous regression in up to 20% of cases, but lack a standard treatment approach. Surgical resection is not favored due to high morbidity and recurrence rates. Systemic therapies have evolved, with tyrosine kinase inhibitors and gamma-secretase inhibitors (GSIs) showing significant clinical benefit. Nirogacestat, a GSI, has recently been approved and is a key treatment option. Other Wnt pathway inhibitors and newer drugs are under development. Cryoablation is also showing promise for extra-abdominal desmoid tumors. The Wnt pathway is central to desmoid tumor pathogenesis, with dysregulation leading to abnormal cell proliferation and fibrosis. The Notch signaling pathway also plays a critical role, and GSIs target substrates in this pathway. Nirogacestat has shown significant efficacy in clinical trials, with high progression-free survival and objective response rates. It causes ovarian dysfunction in some patients, but symptoms resolve upon discontinuation. Other GSIs like AL-101 and AL-102 are under investigation. Sorafenib and pazopanib are also used in treatment. Cryoablation is an attractive option for extra-abdominal desmoid tumors. Overall, systemic therapies like GSIs and tyrosine kinase inhibitors are now preferred for symptomatic patients, while watchful waiting is suitable for asymptomatic cases. The treatment landscape is evolving with new drugs and approaches.