Nanomedicine has shown huge potential in the treatment of cancer, which is not only due to the fact that it can overcome the drawbacks of some small molecular drugs such as insolubility, rapid metabolism, and poor targeting, but also realize the multi modality treatment by containing a variety of molecules. Tremendous novel nano systems referring to above mentioned advantages have been reported so far. However, few newly developed nanomedicine can be approved for clinical applications due to poor stability and rapid metabolism, resulting in the limited efficacy and bottlenecking the development of nanomedicine, that is, "excellent performance in vitro-poor performance in vivo". We believe that the fundamental solution in nanomedicine depends on its basic physical and chemical properties, that is the research and innovation of physical pharmacy theoretical methods of nanopreparation. Herein, focusing on the characteristics of tumor microenvironment and targeting the practical clinical problems, we firstly established a series of physical pharmacy related principles for nanomedicine by the physical and chemical methods combined with the macromolecular Flory-Huggins interaction parameters and scaling theory. Furthermore, taking nanomicelles used to deliver hydrophobic chemotherapeutic drugs as an example, we systemically elaborated the relationship of the physicochemical properties including the carrier composition, self-assembly, drug loading and release, and stability with in vitro and in vivo properties, and explored the related mechanism in vivo.