In order to achieve targeted delivery of anticancer drugs, efficacy improvement, and side effect reduction, various types of nanoparticles are employed. However, their therapeutic effects are not ideal. This phenomenon is caused by tumor microenvironment abnormalities such as abnormal blood vessels, elevated interstitial fluid pressure, and dense extracellular matrix that affect nanoparticle penetration into the tumor's interstitium. Furthermore, nanoparticle properties including size, charge, and shape affect nanoparticle transport into tumors. This review comprehensively goes over the factors hindering nanoparticle penetration into tumors and describes methods for improving nanoparticle distribution by remodeling the tumor microenvironment and optimizing nanoparticle physicochemical properties. Finally, a critical analysis of future development of nanodrug delivery in oncology is further discussed. STATEMENT OF SIGNIFICANCE: This article reviews the factors that hinder the distribution of nanoparticles in tumors, and describes existing methods and approaches for improving the tumor accumulation from the aspects of remodeling the tumor microenvironment and optimizing the properties of nanoparticles. The description of the existing methods and approaches is followed by highlighting their advantages and disadvantages and put forward possible directions for the future researches. At last, the challenges of improving tumor accumulation in nanomedicines design were also discussed. This review will be of great interest to the broad readers who are committed to delivering nanomedicine for cancer treatment.