The administration of nanoparticles(NPs)first faces the challenges of evading renal filtration and clearance of reticuloendothelial system(RES).After that,NPs infiltrate through the expanded endo-thelial space and penetrated the dense stroma of tumor microenvironment to tumor cells.As long as possible to prolong the time of NPs remaining in tumor tissue,NPs release active agent and induce phar-macological action.This review provides a comprehensive summary of the physical and chemical prop-erties of NPs and the influence of various biological factors in tumor microenvironment,and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs.Perspectives and future directions are also provided.