Metal-organic frameworks have the properties of high porosity, variable pore sizes, and easy modification as drug delivery systems. In particular, ZIF-8 based on Zn has been extensively studied in the medical field due to its low toxicity and good biocompatibility. This review introduces the preparation and functional modification of ZIF-8, and its application in drug delivery, focusing on the single-stimulus and multi-stimulus response release of drugs in ZIF-8 materials, the integrated role of diagnosis and treatment with ZIF-8 in cancer treatment, and its application in the synergistic therapy of multiple cancer treatment methods. We summarize the latest developments of ZIF-8 in the field of drug delivery and tumor therapy, and present the main challenges that remain to be resolved in the ZIF-8 drug delivery system.