Tumor microenvironment (TME) plays a critical role in tumorigenesis, tumor invasion and metastasis. TME is composed of stroma, endothelial cells, pericytes, fibroblasts, smooth muscle cells, and immune cells, which is characterized by hypoxia, acidosis, and high interstitial fluid pressure. Due to the important role of TME, we firstly reviewed the composition of TME and discussed the impact of TME on tumor progression, drug and nanoparticle delivery. Next, we reviewed current strategies developed to modulate TME, including modulating tumor vasculature permeability, tumor associated macrophage phenotypes, tumor associated fibroblasts, tumor stroma components, tumor hypoxia, and multiple interventions simultaneously. Also, potential problems and future directions of TME modulation strategy have been discussed.