Cancer treatment has witnessed the emergence of innovative stimuli-responsive nanotherapeutics aiming to overcome limitations associated with traditional drug delivery systems. Metal–organic frameworks (MOFs), a subset of inorganic nanomaterials, are known for their porous structures and versatile applications in integrated cancer diagnosis and therapy. Their noteworthy features include customizable porosity, diverse chemical configurations, adjustable sizes and shapes, and the potential for surface functionalization. The study delved into conventional cancer therapies, provided an overview of MOFs, and discussed various MOF synthesis approaches. Furthermore, this review explored the development of stimuli-responsive MOFs to enhance targeted drug delivery and bioimaging, improving the overall efficacy of cancer treatment, and investigated the applications of stimuli-responsive multifunctional MOFs in nanostructures activated by factors influencing precise drug delivery and bioimaging in cancers. pH, light, ions, temperature, magnetic field, redox reactions, and ATP contribute to the precise control of drug delivery and bioimaging processes. Designed multifunctional MOFs exhibit characteristic changes in response to external and internal stimuli, proving advantageous for drug release and bioimaging. Surface-modified MOFs with responsive features demonstrate excellent biocompatibility with noncancerous cells, efficient drug-loading capabilities, and nanocarrier-mediated targeted drug delivery to cancerous cells. Therefore, the innovative strategy of inorganic nanoscale MOFs with responsive properties holds significant promise for targeted therapeutic drug delivery and imaging across diverse malignancies. The growing interest in stimuli-activated MOFs will open new opportunities in cancer theragnostic applications.