Biliary tract cancers (BTC) are classified according to anatomical sites into gallbladder cancer, intrahepatic bile duct cancer, and extrahepatic bile duct cancer. Their onset is insidious, early diagnosis is difficult, and the prognosis for patients is poor. Surgical treatment, as the only curative treatment method, is not ideal in its effectiveness. Chemotherapy is less effective and its safety is difficult to guarantee for such patients. Targeted therapy has emerged in recent years as a novel treatment modality, targeting specific sites in tumor cells of patients, with significant improvements in both efficacy and safety compared to traditional treatment methods. Vascular endothelial growth factors and their receptors are among the targeted anti-tumor sites expressed in various solid tumors, including BTC, at relatively high levels. When combined, they transmit biological signals into cells through multiple signaling pathways, thereby regulating tumor angiogenesis and hematogenous metastasis. Targeted therapy against vascular endothelial growth factors and their receptors has achieved certain success in BTC. Bevacizumab is the first vascular endothelial growth factor inhibitor used in clinical practice, and its combination with gemcitabine-based systemic chemotherapy, immune checkpoint inhibitors, or tyrosine kinase inhibitors has shown promising results in BTC, although some outcomes have not met expectations, necessitating further clinical trials. Ramucirumab, a vascular endothelial growth factor receptor inhibitor, has been less studied in BTC and is currently only applied in combination with systemic chemotherapy and immune checkpoint inhibitors. Currently, there are various types of tyrosine kinase inhibitors targeting vascular endothelial growth factor and its receptor, such as lenvatinib, sorafenib, apatinib, and anlotinib. Lenvatinib is undoubtedly a focus of research in malignant tumors of the hepatobiliary system. As a multi-target tyrosine kinase inhibitor, lenvatinib combined with immune checkpoint inhibitors and systemic chemotherapy has achieved encouraging efficacy in BTC patients, while ensuring safety to a significant extent. This indicates the direction for future comprehensive treatment methods. Other tyrosine kinase inhibitors such as anlotinib and apatinib also have widely used in BTC. Various targeted drugs have been extensively studied in BTC, and some of them are single-target inhibitors. This suggests to clinical practitioners the importance of fully considering the expression of target sites in patients before administering targeted drugs, in order to achieve precise and maximum therapeutic effects. Future research should focus on both precision treatment and systemic therapy, with the sole goal of improving patient survival and enhancing their quality of life.