Although conventional cancer therapies such as chemotherapy and radiotherapy prevail in clinic, they tend to have narrow therapeutic windows. Many chemotherapies have unfavorable pharmacokinetics while radiotherapy incurs radiotoxicity to normal tissues surrounding tumors. The chemical tunability of supramolecular metal-based nanoparticles (SMNPs) enables the incorporation of various therapeutics, including hydrophilic and hydrophobic chemotherapeutic drugs, photosensitizers, radiosensitizers, and biological therapeutics for more effective delivery to tumors. In this mini-review, we highlight recent advances in SMNPs, namely nanoscale coordination polymers and nanoscale metal-organic frameworks, for drug delivery and cancer therapy. We particularly focus on innovative uses of metal clusters, ligands, pores, and surface modifications to load various therapeutics into SMNPs and critical evaluations of the anticancer efficacies of SMNPs.