The abnormally active tumor vasculature provides a good blood supply for the rapid proliferation of tumors. The tumor microenvironment of tumor cells is associated with the secretion of a lot of angiogenic factors to promote the formation of blood vessels. However, the blood vessels are often irregular and immature. Additionally, the tumor tissue, in the process of its rapid proliferation, oppresses tumor blood vessels, causing hypoperfusion and leading to high interstitial pressure and hypoxia, which also results in changes to the fluid mechanics in the tumor microenvironment. Different fluid mechanics affect circulating tumor cell behavior and control various functions. A good mechanical microenvironment may be one of the important targets for inhibiting tumor proliferation and migration. Therefore, regulating tumor blood vessels to maintain a steady fluid mechanical microenvironment has the potential to be one of the key targets for tumor treatment. Numerous studies have demonstrated that certain natural medicines exhibit significant potential for inhibiting tumor growth and metastasis by selectively targeting tumor blood vessels, regulating the production of angiogenic cytokines, facilitating vascular normalization, etc. Furthermore, natural medicines enhance the anti-tumor effects of chemoradiotherapy and act as adjuvant agents to alleviate its associated side effects. This review summarizes the angiogenesis of the tumor microenvironment, changes induced by mechanical conditions, and the response of tumor cells and vasculature to different fluid shear stress to promote vascular normalization treatment strategies.