The article provides a comprehensive overview of tumor angiogenesis, its mechanisms, and the challenges and opportunities in vascular targeting. Tumor vascularization is a complex process involving multiple biological processes and factors, which can vary between tumor types and anatomical locations. The initiation of tumor angiogenesis, known as the "angiogenic switch," is driven by pro-angiogenic signaling pathways and can be triggered by genetic alterations, tumor-associated inflammation, or immune cell recruitment. Key mechanisms of blood vessel formation in tumors include sprouting angiogenesis, intussusceptive angiogenesis, vasculogenesis, recruitment of endothelial progenitor cells, vascular mimicry, and trans-differentiation of cancer stem cells. Tumor blood vessels exhibit structural and functional abnormalities, such as disorganized networks, reduced blood flow, and increased permeability, which can lead to hypoxia and poor therapeutic outcomes. Pro-angiogenic factors like VEGF, FGF-2, PDGF, angiopoietins, ephrins, apelin, and chemokines play crucial roles in tumor angiogenesis. The article also discusses the contributions of immune cells, particularly macrophages, to tumor angiogenesis and endothelial cell remodeling. Despite the development of anti-angiogenic therapies, their efficacy has been limited due to tumor resistance and the heterogeneity of tumor vessels. The review highlights the need for further research to understand the molecular and functional heterogeneities of tumor vessels and to develop more effective strategies for vascular targeting in cancer therapy.The article provides a comprehensive overview of tumor angiogenesis, its mechanisms, and the challenges and opportunities in vascular targeting. Tumor vascularization is a complex process involving multiple biological processes and factors, which can vary between tumor types and anatomical locations. The initiation of tumor angiogenesis, known as the "angiogenic switch," is driven by pro-angiogenic signaling pathways and can be triggered by genetic alterations, tumor-associated inflammation, or immune cell recruitment. Key mechanisms of blood vessel formation in tumors include sprouting angiogenesis, intussusceptive angiogenesis, vasculogenesis, recruitment of endothelial progenitor cells, vascular mimicry, and trans-differentiation of cancer stem cells. Tumor blood vessels exhibit structural and functional abnormalities, such as disorganized networks, reduced blood flow, and increased permeability, which can lead to hypoxia and poor therapeutic outcomes. Pro-angiogenic factors like VEGF, FGF-2, PDGF, angiopoietins, ephrins, apelin, and chemokines play crucial roles in tumor angiogenesis. The article also discusses the contributions of immune cells, particularly macrophages, to tumor angiogenesis and endothelial cell remodeling. Despite the development of anti-angiogenic therapies, their efficacy has been limited due to tumor resistance and the heterogeneity of tumor vessels. The review highlights the need for further research to understand the molecular and functional heterogeneities of tumor vessels and to develop more effective strategies for vascular targeting in cancer therapy.