This review discusses the development and application of targeted drug delivery systems (TDLS) for tumor therapy, focusing on different targeting ligands such as folic acid, carbohydrates, peptides, aptamers, and antibodies. Traditional cancer treatments often harm both tumor and normal cells, leading to significant systemic toxicity. TDLS aim to improve therapeutic efficacy while minimizing side effects by specifically targeting cancer cells. The review summarizes recent advancements in TDLS, highlighting the advantages, challenges, and future prospects of these systems. Folic acid, a small-molecule vitamin, is widely used as a targeting ligand due to its high expression in many cancers. Folate-drug conjugates and folate-conjugated nanoparticles have shown promising results in cancer therapy. However, clinical trials face challenges such as drug resistance and toxicity. Carbohydrates, including glucose, galactose, and hyaluronic acid, are effective targeting ligands due to their ability to bind to specific receptors on cancer cells. Carbohydrate-drug conjugates and carbohydrate-conjugated nanoparticles have demonstrated enhanced therapeutic efficacy and reduced toxicity. However, further research is needed to fully understand their role and optimize their application. Peptides, with their small size and high affinity for cell receptors, are effective targeting ligands. Peptide-drug conjugates and peptide-conjugated nanoparticles have shown improved therapeutic outcomes. However, challenges such as heterogeneity of tumor tissues and drug degradation remain. Aptamers, which are short nucleic acid sequences, offer high specificity and affinity. Aptamer-drug conjugates and aptamer-conjugated nanoparticles have shown promising results in cancer therapy. However, their clinical translation is limited by issues such as low in vivo specificity and rapid clearance. Antibodies, with their high specificity, are effective targeting ligands. Antibody-drug conjugates (ADCs) and antibody-conjugated nanoparticles have shown significant therapeutic benefits. However, challenges such as poor tumor penetration and immune responses remain. The review concludes that TDLS offer a promising approach for cancer therapy, but further research is needed to overcome challenges such as drug resistance, toxicity, and clinical translation. Future research should focus on improving targeting specificity, reducing side effects, and enhancing the efficiency of TDLS. The development of new targeting ligands and optimization of delivery systems will be crucial for advancing cancer therapy.This review discusses the development and application of targeted drug delivery systems (TDLS) for tumor therapy, focusing on different targeting ligands such as folic acid, carbohydrates, peptides, aptamers, and antibodies. Traditional cancer treatments often harm both tumor and normal cells, leading to significant systemic toxicity. TDLS aim to improve therapeutic efficacy while minimizing side effects by specifically targeting cancer cells. The review summarizes recent advancements in TDLS, highlighting the advantages, challenges, and future prospects of these systems. Folic acid, a small-molecule vitamin, is widely used as a targeting ligand due to its high expression in many cancers. Folate-drug conjugates and folate-conjugated nanoparticles have shown promising results in cancer therapy. However, clinical trials face challenges such as drug resistance and toxicity. Carbohydrates, including glucose, galactose, and hyaluronic acid, are effective targeting ligands due to their ability to bind to specific receptors on cancer cells. Carbohydrate-drug conjugates and carbohydrate-conjugated nanoparticles have demonstrated enhanced therapeutic efficacy and reduced toxicity. However, further research is needed to fully understand their role and optimize their application. Peptides, with their small size and high affinity for cell receptors, are effective targeting ligands. Peptide-drug conjugates and peptide-conjugated nanoparticles have shown improved therapeutic outcomes. However, challenges such as heterogeneity of tumor tissues and drug degradation remain. Aptamers, which are short nucleic acid sequences, offer high specificity and affinity. Aptamer-drug conjugates and aptamer-conjugated nanoparticles have shown promising results in cancer therapy. However, their clinical translation is limited by issues such as low in vivo specificity and rapid clearance. Antibodies, with their high specificity, are effective targeting ligands. Antibody-drug conjugates (ADCs) and antibody-conjugated nanoparticles have shown significant therapeutic benefits. However, challenges such as poor tumor penetration and immune responses remain. The review concludes that TDLS offer a promising approach for cancer therapy, but further research is needed to overcome challenges such as drug resistance, toxicity, and clinical translation. Future research should focus on improving targeting specificity, reducing side effects, and enhancing the efficiency of TDLS. The development of new targeting ligands and optimization of delivery systems will be crucial for advancing cancer therapy.