Metal–organic frameworks (MOFs) have become a potential material in cancer therapy because of their unique porosity and customisable features. These materials provide novel approaches to targeted treatment, imaging, and drug administration. The potential of MOFs has been further boosted by the addition of stimuli-responsive components, which allow for the regulated release of medicinal compounds in response to particular biological or environmental triggers. This chapter explores the principles of stimulus-responsive MOFs, explaining their basic structure, processes of response, and the range of stimuli, including pH, temperature, enzymes, and light, that can be used to treat cancer. It demonstrates how these cutting-edge materials are being used to create more effective and focused drug delivery systems, enhance imaging methods, and achieve accurate tumour targeting with negligible side effects through a thorough examination of their uses. It also discusses important elements of toxicity and biocompatibility, offering information from studies conducted in vivo and in vitro as well as regulatory considerations. The potential for stimuli-responsive MOFs to transform cancer therapy is highlighted in the chapter’s discussion of emerging trends, future opportunities for innovation, and current obstacles facing the field.