The tumor microenvironment (TME) is a complex mixture of cell types, including tumor cells, immune cells, and endothelial cells (ECs). ECs play a crucial role in controlling blood fluidity, permeability, and angiogenesis, while also regulating the antitumor immune response. Tumor-associated ECs (TAECs) exhibit abnormal phenotypes and functions compared to normal ECs, characterized by high proliferative potential and the ability to activate immunosuppressive mechanisms. TAECs are involved in T cell priming, activation, and proliferation, and contribute to the development of tertiary lymphoid structures (TLS), which enhance responses to immune checkpoint inhibitors (ICI). The study aims to explore the critical role of ECs within the TME, focusing on their interactions with immune cells and their impact on immunotherapy. TAECs display stem cell-like properties, undergo endothelial-to-mesenchymal transition (EndMT), and exhibit altered gene expression profiles and chromosomal instability. They regulate immune cell recruitment, activation, and antigen presentation, and can establish selective barriers that favor regulatory T (Treg) cell traffic while repressing effector immune cells. TAECs also interact with tumor-associated macrophages (TAMs) and B cells, enhancing metastatic potential and promoting angiogenesis. The formation of TLS in the TME is associated with better outcomes in various cancers, and the presence of preexisting TLS improves responses to ICI. Targeting TAECs may improve cancer therapy by enhancing antitumor immune responses and disrupting tumor progression.The tumor microenvironment (TME) is a complex mixture of cell types, including tumor cells, immune cells, and endothelial cells (ECs). ECs play a crucial role in controlling blood fluidity, permeability, and angiogenesis, while also regulating the antitumor immune response. Tumor-associated ECs (TAECs) exhibit abnormal phenotypes and functions compared to normal ECs, characterized by high proliferative potential and the ability to activate immunosuppressive mechanisms. TAECs are involved in T cell priming, activation, and proliferation, and contribute to the development of tertiary lymphoid structures (TLS), which enhance responses to immune checkpoint inhibitors (ICI). The study aims to explore the critical role of ECs within the TME, focusing on their interactions with immune cells and their impact on immunotherapy. TAECs display stem cell-like properties, undergo endothelial-to-mesenchymal transition (EndMT), and exhibit altered gene expression profiles and chromosomal instability. They regulate immune cell recruitment, activation, and antigen presentation, and can establish selective barriers that favor regulatory T (Treg) cell traffic while repressing effector immune cells. TAECs also interact with tumor-associated macrophages (TAMs) and B cells, enhancing metastatic potential and promoting angiogenesis. The formation of TLS in the TME is associated with better outcomes in various cancers, and the presence of preexisting TLS improves responses to ICI. Targeting TAECs may improve cancer therapy by enhancing antitumor immune responses and disrupting tumor progression.