Cancers represent one of the most major causes of mortality worldwide. Solid tumors which are the most prevalent cancers have a complex microenvironment where neovascularization reduces the efficiency of anti-tumor treatments. Thus, advanced selective anti-cancer therapies targeting the neovascularization are required. Strategies targeting neovascularization are different by the nature of their target: molecular (pro-angiogenic growth factors or their receptors) or cellular (endothelial cells, endothelial progenitor or stem cells). The targeting nano-formulations are the most promising strategy. The size of nanoparticles promotes an adequate diffusion within the tumor despite of its abnormal vasculature and their accumulation. This selective therapies supported by nanotechnologies would help to take up the challenge of reducing tumor aggressiveness by targeting and normalizing its vascularization. Monotherapy targeting neo-vascularization is not suitable with the complexity of microenvironment. Their association with different anti-tumor selective therapies is required. New three-dimensional microfluidic models appear to be particularly adequate to evaluate the efficiency of anti-angiogenic therapies and the synergistic effect of their associations.