Abstract: The complexity of tumor microenvironment brings both challenges and opportunities for targeted drug delivery. On the one hand, using the special characteristic as stimuli, we can construct a variety of responsive drug delivery systems for tumor targeting. On the other hand, the abnormal vasculature and dense extracellular matrix in solid tumor become formidable barriers to the nanoparticles delivery, which greatly reduces the drug delivery efficiency. Lots of researches focus on regulating the tumor microenvironment to make it more conducive to drug delivery. In this review, we will highlight the recent advances both in tumor microenvironment responsive nano-drug delivery systems design and tumor microenvironment regulation to improve tumor targeted delivery efficiency, and discuss the existing problems and future development.