In tumors, the blood supply is anisotropic spatially and temporally, meanwhile the vascular permeability is high and the ability of fluid flowing from lymphangion is poor. These factors work together to create tumor microenvironment and block therapeutic agents from uniformly delivering into tumors. Compared to conventional medicine, nanomedicine has the potential to enable the preferential delivery of drugs to tumor, deliver more than one therapeutic agent, and bind drugs to target cancer cells specially. But the specific physiological barriers presented in tumor hinder efficient and uniform delivery of nanoparticles into tumors. This may be account for moderate survival benefit obtained from FDA-approved nanomedicines. Here, we summarize these barriers existing in cancer therapy and researches aiming at conquering these barriers. Finally, we discuss factors in nanoparticles design to improve delivering efficiency for tumor.