Abstract: Nano-drug delivery systems(nano-DDSs)play an important role in targeted cancer therapy. Due to the physiological characteristics of the body and the heterogenicity of tumor, intravenous delivery of anticancer agents carried by nano-DDSs from the injection site to their targeted sites is required to overcome multiple physiological and pathological barriers, including blood, tumor tissue, tumor cell and intracellular transportation. This review surveys emerging strategies for the development of novel nano-DDSs that can conquer the physiological and pathological barriers of tumor, which provides a great potential platform for safe and efficient cancer treatment.