Book excerpt: Cancer drug resistance has become one of the main challenges for the failure of chemotherapy, greatly limiting the selection and use of anticancer drugs and dashing the hopes of cancer patients. The emergence of supramolecular host-guest nanosystems has brought the field of supramolecular chemistry into the nanoworld, providing a potential solution to this challenge. Compared with conventional chemotherapeutic platforms, supramolecular host-guest nanosystems can reverse cancer drug resistance by increasing drug uptake, reducing drug efflux, activating drugs, and inhibiting DNA repair. Herein, we summarize the research progress of supramolecular host-guest nanosystems for overcoming cancer drug resistance and discuss the future research direction in this field. It is hoped that this review will provide more positive references for overcoming cancer drug resistance and promoting the development of supramolecular host-guest nanosystems.