Metal–drug coordination nanoparticles and hydrogels offer enhanced drug delivery through the use of drug molecules as ligands to form coordination bonds with metal ions. This approach allows for a higher drug-to-metal ratio compared to conventional adsorption-based strategies, resulting in materials with lower metal content and improved therapeutic efficacy. The review discusses the formation of various nanomaterials and soft materials using small-molecule drugs, nucleic acids, and proteins. These materials can be functionalized with targeting ligands to improve delivery efficiency and reduce toxicity. Applications include cancer, viral, bacterial, inflammatory bowel, and bone diseases. Metal–drug coordination provides advantages such as low metal content, altered lipophilicity, responsiveness to disease microenvironments, and synergistic therapeutic effects. Coordination bonds between metal ions and drug molecules are stable yet reversible, enabling controlled drug release. Metal ions like Fe²⁺, Ca²⁺, and Zn²⁺ are biocompatible and can be used to form nanoparticles and hydrogels. Metal–drug coordination materials can respond to physiological conditions such as pH, redox status, and enzymatic activity, enhancing targeted delivery. Examples include coordination-based NPs for cancer therapy, hydrogels for drug release, and materials for imaging and therapy. The review highlights the potential of metal–drug coordination in drug delivery, emphasizing its advantages over traditional inorganic nanomaterials. The use of metal ions in coordination with drugs allows for the development of materials with enhanced stability, controlled release, and reduced toxicity. The review also discusses the formation of various materials, including MOFs, hydrogels, and NPs, and their applications in therapeutic settings. The study emphasizes the importance of understanding the coordination mechanisms and the role of metal ions in enhancing drug delivery and therapeutic outcomes.Metal–drug coordination nanoparticles and hydrogels offer enhanced drug delivery through the use of drug molecules as ligands to form coordination bonds with metal ions. This approach allows for a higher drug-to-metal ratio compared to conventional adsorption-based strategies, resulting in materials with lower metal content and improved therapeutic efficacy. The review discusses the formation of various nanomaterials and soft materials using small-molecule drugs, nucleic acids, and proteins. These materials can be functionalized with targeting ligands to improve delivery efficiency and reduce toxicity. Applications include cancer, viral, bacterial, inflammatory bowel, and bone diseases. Metal–drug coordination provides advantages such as low metal content, altered lipophilicity, responsiveness to disease microenvironments, and synergistic therapeutic effects. Coordination bonds between metal ions and drug molecules are stable yet reversible, enabling controlled drug release. Metal ions like Fe²⁺, Ca²⁺, and Zn²⁺ are biocompatible and can be used to form nanoparticles and hydrogels. Metal–drug coordination materials can respond to physiological conditions such as pH, redox status, and enzymatic activity, enhancing targeted delivery. Examples include coordination-based NPs for cancer therapy, hydrogels for drug release, and materials for imaging and therapy. The review highlights the potential of metal–drug coordination in drug delivery, emphasizing its advantages over traditional inorganic nanomaterials. The use of metal ions in coordination with drugs allows for the development of materials with enhanced stability, controlled release, and reduced toxicity. The review also discusses the formation of various materials, including MOFs, hydrogels, and NPs, and their applications in therapeutic settings. The study emphasizes the importance of understanding the coordination mechanisms and the role of metal ions in enhancing drug delivery and therapeutic outcomes.