This review article discusses the challenges and recent advancements in transvascular transport of nanocarriers (NCs) for tumor delivery. NCs are crucial for delivering theranostic agents to tumors, but their low delivery efficiency remains a major challenge. Transvascular transport is a key pathway for NC delivery, yet the interactions between NCs and vascular systems are not fully understood. The review highlights various delivery mechanisms, including the enhanced permeability and retention (EPR) effect, active transcytosis, and cell/bacteria-mediated delivery. Strategies to enhance transvascular transport are explored, offering solutions across physicochemical, biological, and pharmacological domains. A forward-looking delivery framework is proposed, incorporating advanced tumor/vessel models, high-throughput NC libraries, nano-bio interaction datasets, and artificial intelligence to guide the design of next-generation carriers. The EPR effect, which was postulated in 1986, is a key mechanism for NC delivery, but its clinical translation has been limited. Recent studies suggest that the basement membrane surrounding tumor vessels is a critical barrier for NC delivery based on the EPR effect. Active transcytosis, which involves the transport of NCs through endothelial cells, has been shown to be a dominant mechanism for vascular extravasation. Cell and bacterial-mediated delivery strategies, which utilize the intrinsic inflammatory responsiveness or tumor-tropism of cells and bacteria, have also been explored to improve transvascular transport. The review discusses the mechanisms of active transcytosis, including caveolae-dependent endocytosis and exocytosis, and highlights the importance of understanding the interactions between NCs and vascular endothelium. It also explores the role of specific endothelial cells, such as nanoparticle transport endothelial cells (N-TECs), in transvascular transport. Additionally, the review discusses the potential of cell and bacterial-mediated delivery systems, which can bypass the vascular barrier and improve tumor delivery. The review also addresses the challenges of clinical translation of nanomedicines, including the need for standardized preclinical research, tumor/vessel models, and patient stratification. The integration of AI and big data management is highlighted as a promising approach to optimize NC design and delivery. Finally, the review emphasizes the importance of creating an authoritative NC library to collect validated NCs and guide the design of next-generation carriers. The review concludes that a deeper understanding of transvascular transport and tumor delivery of NCs is essential for advancing cancer nanomedicine.This review article discusses the challenges and recent advancements in transvascular transport of nanocarriers (NCs) for tumor delivery. NCs are crucial for delivering theranostic agents to tumors, but their low delivery efficiency remains a major challenge. Transvascular transport is a key pathway for NC delivery, yet the interactions between NCs and vascular systems are not fully understood. The review highlights various delivery mechanisms, including the enhanced permeability and retention (EPR) effect, active transcytosis, and cell/bacteria-mediated delivery. Strategies to enhance transvascular transport are explored, offering solutions across physicochemical, biological, and pharmacological domains. A forward-looking delivery framework is proposed, incorporating advanced tumor/vessel models, high-throughput NC libraries, nano-bio interaction datasets, and artificial intelligence to guide the design of next-generation carriers. The EPR effect, which was postulated in 1986, is a key mechanism for NC delivery, but its clinical translation has been limited. Recent studies suggest that the basement membrane surrounding tumor vessels is a critical barrier for NC delivery based on the EPR effect. Active transcytosis, which involves the transport of NCs through endothelial cells, has been shown to be a dominant mechanism for vascular extravasation. Cell and bacterial-mediated delivery strategies, which utilize the intrinsic inflammatory responsiveness or tumor-tropism of cells and bacteria, have also been explored to improve transvascular transport. The review discusses the mechanisms of active transcytosis, including caveolae-dependent endocytosis and exocytosis, and highlights the importance of understanding the interactions between NCs and vascular endothelium. It also explores the role of specific endothelial cells, such as nanoparticle transport endothelial cells (N-TECs), in transvascular transport. Additionally, the review discusses the potential of cell and bacterial-mediated delivery systems, which can bypass the vascular barrier and improve tumor delivery. The review also addresses the challenges of clinical translation of nanomedicines, including the need for standardized preclinical research, tumor/vessel models, and patient stratification. The integration of AI and big data management is highlighted as a promising approach to optimize NC design and delivery. Finally, the review emphasizes the importance of creating an authoritative NC library to collect validated NCs and guide the design of next-generation carriers. The review concludes that a deeper understanding of transvascular transport and tumor delivery of NCs is essential for advancing cancer nanomedicine.