Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Extensive heterogeneity exists in the clinical course and prognosis of GISTs due to multiple genetic mutations. Since the advent of tyrosine kinase inhibitors (TKIs), such as imatinib, the survival of patients with GISTs has substsntially improved. However, progression or metastasis often occurs in these patients. For advanced and metastatic GISTs, drug selection and surgical indications have been studied and debated in recent years. With further research in etiology and TKI resistance, novel target agents such as ripretinib, avapritinib, and other pathway inhibitors have been introduced into clinical practice, enabling a more individualized and accurate treatment modality for advanced and metastatic GISTs. This review provides an update on the current therapeutic development landscape in advanced and metastatic GISTs.