Metal-organic frameworks (MOFs), as a prominent category of hybrid porous materials constructed from metal clusters or ions with organic linkers, have been broadly employed as controlled systems of drug delivery due to their inherent interesting properties. These properties, such as high loading capability and tremendous biocompatibility, offer an exceptional opportunity for the treatment of cancer. In this review, we focus on the latest advancement of smart MOFs as systems of drug delivery for cancer treatment, diagnosis or both (theranostics). Furthermore, different methods and strategies for synthesizing smart MOFs with various mechanisms of drug release under diverse stimuli, such as pH, temperature, redox, magnetic field, enzyme, and light, were summarized and discussed. The current review helps in a better understanding of smart MOFs systems that would be useful for their smart design toward medical applications.