Introduction: Modern comprehensive studies of tumor microenvironment changes allowed scientists to develop new and more efficient strategies that will improve anticancer drug delivery on site. The tumor microenvironment, especially the dense extracellular matrix, has a recognized capability to hamper the penetration of conventional drugs. Development and co-applications of strategies aiming at remodeling the tumor microenvironment are highly demanded to improve drug delivery at the tumor site in a therapeutic prospect. Areas covered: Increasing indications suggest that classical physical approaches such as exposure to ionizing radiations, hyperthermia or light irradiation, and emerging ones as sonoporation, electric field or cold plasma technology can be applied as standalone or associated strategies to remodel the tumor microenvironment. The impacts on vasculature and extracellular matrix remodeling of these physical approaches will be discussed with the goal to improve nanotherapeutics delivery at the tumor site. Expert opinion: Physical approaches to modulate vascular properties and remodel the extracellular matrix are of particular interest to locally control and improve drug delivery and thus increase its therapeutic index. They are particularly powerful as adjuvant to nanomedicine delivery; the development of these technologies could have extremely widespread implications for cancer treatment.