Nanomedicines are widely explored for cancer therapy, aiming to improve drug efficacy and reduce toxicity by delivering drugs more efficiently to pathological sites while minimizing accumulation in healthy tissues. Over 20 cancer nanomedicines are currently approved for clinical use, with hundreds more in development. Key challenges in nanomedicine tumor targeting include biological barriers and pathophysiological heterogeneity. This manuscript reviews the principles, progress, and products in nanomedicine tumor targeting, identifies current problems and challenges, and discusses future prospects. Cancer therapy relies on various treatments, including surgery, radiotherapy, chemotherapy, molecularly targeted therapy, hormone therapy, and immunotherapy. The choice of treatment depends on tumor type, location, stage, and patient well-being. Complete tumor removal is the ultimate goal, but advanced cancers often invade healthy tissues and metastasize, complicating treatment. Anticancer drugs often have moderate effectiveness due to poor accumulation in tumors and metastases, as well as severe side effects from their large volume of distribution. To improve therapeutic outcomes, various drug delivery systems have been developed, including liposomes, polymers, proteins, micelles, and nanomaterials. Nanomedicine tumor targeting is traditionally based on the enhanced permeability and retention (EPR) effect, which describes the prolonged circulation time of macromolecules in the blood, leading to increased accumulation in tumors. However, EPR-based targeting has limitations, such as varying tumor vascular permeability and transcytosis. Recent studies have expanded on EPR by considering active energy-dependent transcytosis and the role of circulating phagocytes. Despite these advancements, passive targeting remains challenging due to inter-tumor and intra-tumor heterogeneity. Physical and pharmacological priming techniques, such as ultrasound, microbubbles, and pharmacological agents, can enhance passive targeting. Active targeting involves the use of recognition motifs that bind to receptors on cancer cells, tumor endothelial cells, or other cells in the tumor microenvironment. Antibodies, peptides, and other biotechnological carriers are commonly used for active targeting. The field of antibody-drug conjugates (ADCs) has seen significant progress, with multiple products approved for clinical use. Peptides, such as Lutathera, have also shown promise in radionuclide delivery. Nature-inspired active targeting strategies, such as using small-sized carrier materials (5-35 nm), have been explored to improve tumor targeting efficiency. Several nanomedicine formulations have been approved for clinical use, including liposomal doxorubicin (Doxil/Caelyx), albumin-based Abraxane, and inorganic nanoparticles like NanoTherm and Hensify. These formulations have primarily reduced side effects rather than improved therapeutic efficacy. Promising platform technologies in clinical trials include ThermoDox, a temperature-responsive liposome formulation, and polymeric micelles, which have shown potential in multi-drug delivery and synergistic effects. The clinical translation ofNanomedicines are widely explored for cancer therapy, aiming to improve drug efficacy and reduce toxicity by delivering drugs more efficiently to pathological sites while minimizing accumulation in healthy tissues. Over 20 cancer nanomedicines are currently approved for clinical use, with hundreds more in development. Key challenges in nanomedicine tumor targeting include biological barriers and pathophysiological heterogeneity. This manuscript reviews the principles, progress, and products in nanomedicine tumor targeting, identifies current problems and challenges, and discusses future prospects. Cancer therapy relies on various treatments, including surgery, radiotherapy, chemotherapy, molecularly targeted therapy, hormone therapy, and immunotherapy. The choice of treatment depends on tumor type, location, stage, and patient well-being. Complete tumor removal is the ultimate goal, but advanced cancers often invade healthy tissues and metastasize, complicating treatment. Anticancer drugs often have moderate effectiveness due to poor accumulation in tumors and metastases, as well as severe side effects from their large volume of distribution. To improve therapeutic outcomes, various drug delivery systems have been developed, including liposomes, polymers, proteins, micelles, and nanomaterials. Nanomedicine tumor targeting is traditionally based on the enhanced permeability and retention (EPR) effect, which describes the prolonged circulation time of macromolecules in the blood, leading to increased accumulation in tumors. However, EPR-based targeting has limitations, such as varying tumor vascular permeability and transcytosis. Recent studies have expanded on EPR by considering active energy-dependent transcytosis and the role of circulating phagocytes. Despite these advancements, passive targeting remains challenging due to inter-tumor and intra-tumor heterogeneity. Physical and pharmacological priming techniques, such as ultrasound, microbubbles, and pharmacological agents, can enhance passive targeting. Active targeting involves the use of recognition motifs that bind to receptors on cancer cells, tumor endothelial cells, or other cells in the tumor microenvironment. Antibodies, peptides, and other biotechnological carriers are commonly used for active targeting. The field of antibody-drug conjugates (ADCs) has seen significant progress, with multiple products approved for clinical use. Peptides, such as Lutathera, have also shown promise in radionuclide delivery. Nature-inspired active targeting strategies, such as using small-sized carrier materials (5-35 nm), have been explored to improve tumor targeting efficiency. Several nanomedicine formulations have been approved for clinical use, including liposomal doxorubicin (Doxil/Caelyx), albumin-based Abraxane, and inorganic nanoparticles like NanoTherm and Hensify. These formulations have primarily reduced side effects rather than improved therapeutic efficacy. Promising platform technologies in clinical trials include ThermoDox, a temperature-responsive liposome formulation, and polymeric micelles, which have shown potential in multi-drug delivery and synergistic effects. The clinical translation of