This review discusses the advancements in targeted drug delivery systems for tumor therapy, focusing on various targeting ligands such as folic acid, carbohydrates, peptides, aptamers, and antibodies. Each ligand is evaluated for its structural diversity, advantages, and challenges in distinguishing between pathological and normal tissues. The review highlights the potential of these ligands in creating targeted drug delivery systems that can selectively deliver drugs to cancer cells, enhancing therapeutic efficacy while reducing toxicity. 1. **Folate-Mediated Targeted Drug Delivery System**: Folic acid is used to target tumor cells overexpressing the folate receptor, either by conjugating it to small molecule drugs or combining it with nanomaterials. This approach has shown promising results in enhancing drug delivery and reducing toxicity. 2. **Carbohydrate-Mediated Targeted Drug Delivery System**: Carbohydrates, such as glucose and galactose, are used to target cancer cells with high glucose metabolism. Glycoconjugates, which are linked to anticancer drugs, have demonstrated enhanced cytotoxicity and reduced toxicity in preclinical studies. 3. **Peptide-Mediated Targeted Drug Delivery System**: Peptides, including tumor targeting peptides and cell-penetrating peptides, are used to enhance drug delivery and therapeutic efficacy. Peptide-drug conjugates and peptide-conjugated nanoparticles have shown promising results in preclinical trials but face challenges in clinical translation. 4. **Aptamer-Mediated Targeted Drug Delivery System**: Nucleic acid aptamers, known as chemical antibodies, are used to target specific biomarkers. Aptamer-drug conjugates and aptamer-conjugated nanoparticles have shown potential in cancer therapy but need further development to improve specificity and stability. 5. **Antibody-Mediated Targeted Drug Delivery System**: Monoclonal antibodies (mAbs) are used to target cancer-specific antigens. Antibody-drug conjugates (ADCs) and antibody-conjugated nanoparticles have been approved for clinical use and show promise in enhancing therapeutic outcomes. The review concludes by discussing the future prospects and challenges of targeted drug delivery systems, emphasizing the need for further research to improve targeting specificity, reduce toxicity, and enhance clinical translational efficiency.This review discusses the advancements in targeted drug delivery systems for tumor therapy, focusing on various targeting ligands such as folic acid, carbohydrates, peptides, aptamers, and antibodies. Each ligand is evaluated for its structural diversity, advantages, and challenges in distinguishing between pathological and normal tissues. The review highlights the potential of these ligands in creating targeted drug delivery systems that can selectively deliver drugs to cancer cells, enhancing therapeutic efficacy while reducing toxicity. 1. **Folate-Mediated Targeted Drug Delivery System**: Folic acid is used to target tumor cells overexpressing the folate receptor, either by conjugating it to small molecule drugs or combining it with nanomaterials. This approach has shown promising results in enhancing drug delivery and reducing toxicity. 2. **Carbohydrate-Mediated Targeted Drug Delivery System**: Carbohydrates, such as glucose and galactose, are used to target cancer cells with high glucose metabolism. Glycoconjugates, which are linked to anticancer drugs, have demonstrated enhanced cytotoxicity and reduced toxicity in preclinical studies. 3. **Peptide-Mediated Targeted Drug Delivery System**: Peptides, including tumor targeting peptides and cell-penetrating peptides, are used to enhance drug delivery and therapeutic efficacy. Peptide-drug conjugates and peptide-conjugated nanoparticles have shown promising results in preclinical trials but face challenges in clinical translation. 4. **Aptamer-Mediated Targeted Drug Delivery System**: Nucleic acid aptamers, known as chemical antibodies, are used to target specific biomarkers. Aptamer-drug conjugates and aptamer-conjugated nanoparticles have shown potential in cancer therapy but need further development to improve specificity and stability. 5. **Antibody-Mediated Targeted Drug Delivery System**: Monoclonal antibodies (mAbs) are used to target cancer-specific antigens. Antibody-drug conjugates (ADCs) and antibody-conjugated nanoparticles have been approved for clinical use and show promise in enhancing therapeutic outcomes. The review concludes by discussing the future prospects and challenges of targeted drug delivery systems, emphasizing the need for further research to improve targeting specificity, reduce toxicity, and enhance clinical translational efficiency.