Nanocarriers (NCs) play a crucial role in delivering theranostic agents to tumors, but their low delivery efficiency remains a significant challenge. Transvascular transport is a critical pathway for NC delivery from vessels to tumors, and recent advancements have clarified various mechanisms, including the enhanced permeability and retention effect (EPR), cooperative immune-driven effects, active transcytosis, and cell/bacteria-mediated delivery. The EPR effect, while initially promising, has been questioned due to the dense basement membrane surrounding tumor vessels, which hinders NC extravasation. Active transcytosis, mediated by caveolae-dependent endocytosis and exocytosis, has emerged as a dominant mechanism for NC delivery, particularly in low-permeability tumor vessels. Cell/bacteria-mediated delivery, leveraging the inflammatory responsiveness or tumor-tropism of cells and bacteria, offers promising solutions to overcome biological barriers. Future research should focus on optimizing these mechanisms, developing advanced tumor and vessel models, and integrating AI and big data to enhance the clinical translation of nanomedicine. Standardization of preclinical research and the creation of a comprehensive NC library are also essential for advancing the field.Nanocarriers (NCs) play a crucial role in delivering theranostic agents to tumors, but their low delivery efficiency remains a significant challenge. Transvascular transport is a critical pathway for NC delivery from vessels to tumors, and recent advancements have clarified various mechanisms, including the enhanced permeability and retention effect (EPR), cooperative immune-driven effects, active transcytosis, and cell/bacteria-mediated delivery. The EPR effect, while initially promising, has been questioned due to the dense basement membrane surrounding tumor vessels, which hinders NC extravasation. Active transcytosis, mediated by caveolae-dependent endocytosis and exocytosis, has emerged as a dominant mechanism for NC delivery, particularly in low-permeability tumor vessels. Cell/bacteria-mediated delivery, leveraging the inflammatory responsiveness or tumor-tropism of cells and bacteria, offers promising solutions to overcome biological barriers. Future research should focus on optimizing these mechanisms, developing advanced tumor and vessel models, and integrating AI and big data to enhance the clinical translation of nanomedicine. Standardization of preclinical research and the creation of a comprehensive NC library are also essential for advancing the field.