During tumor development, the tumor itself must continuously generate new blood vessels to meet their growth needs while also allowing for tumor invasion and metastasis. One of the most common features of tumors is hypoxia, which drives the process of tumor angiogenesis by regulating the tumor microenvironment, thus adversely affecting the prognosis of patients. In addition, to overcome unsuitable environments for growth, such as hypoxia, nutrient deficiency, hyperacidity, and immunosuppression, the tumor microenvironment (TME) coordinates angiogenesis in several ways to restore the supply of oxygen and nutrients and to remove metabolic wastes. A growing body of research suggests that tumor angiogenesis and hypoxia interact through a complex interplay of crosstalk, which is inextricably linked to the TME. Here, we review the TME's positive contribution to angiogenesis from an angiogenesis-centric perspective while considering the objective impact of hypoxic phenotypes and the status and limitations of current angiogenic therapies. Display omitted •A close interactive link exists between tumor angiogenesis, hypoxia, and TME, collectively promoting tumorigenesis and progression.•Growth factors in the tumor microenvironment are secreted and regulated by various cell types, and a significant correlation exists between their expression levels and hypoxia.•The development of anti-angiogenic therapy is hampered by the lack of accurate biomarkers, the uncertain time window of medication, and the widespread problem of drug resistance.