Medical applications of nanoparticular systems have attracted considerable attention because of their potential use in therapeutic targeting of disease tissues and their lower level of toxicity against healthy tissue, relative to traditional pharmaceutical drugs. The use of nanoparticular systems has been shown to overcome the limitations of most anticancer drugs in clinical applications. In particular, the improved performance of smarted nanoparticular system for solving the drug resistance problems that typically interrupt tumor treatment has provided a promising strategy for successful tumor chemotherapy. This review highlights recent studies that have examined the therapeutic effect of nanoparticular systems on drug-resistant tumors and presents insight on how they work.