Multi-drug resistance (MDR) refers to the phenomenon that tumor cells product resistant to traditional and new chemotherapeutic drugs, which has become an important obstacle in the treatment of malignant tumors. In recent years, it has been found that nanoscale drug delivery systems (NDDS) have unique advantages in inhibiting tumor multi-drug resistance, including increasing the solubility and stability of drugs, avoiding drug efflux pumps, achieving higher drug concentrations at the target site via using lower doses and negligible toxic side effects. Therefore, NDDS emerge as an effective strategy to overcome MDR in cancer. Here, we review the types and research progress of NDDS for enhancing the uptake of anticancer drugs and selective intracellular accumulation, including targeting specific ligand functionalization systems and stimulus-responsive drug activation and release systems.