While intraperitoneal (IP) therapy of ovarian cancer is a theoretically promising treatment option, it is not clinically well accepted due to the several challenges in IP drug delivery. Nanoparticles are promising drug carriers, which may alleviate the difficulties in IP chemotherapy. However, currently available nanoparticles need to be further improved to fulfill the following requirements: (i) they must remain non-interactive with normal cells and prevent the payload from premature leaking; (ii) once the drug carriers reach the tumor, they should enter the cells efficiently and release the drug in the cells to effectively kill the targeted cells. Our recent observation indicates that a popular nanoparticle system fails these expectations by large margin. For safe and effective IP chemotherapy, new types of carriers and/or surface modification strategies are urgently needed.