In the design process of rocket, airplane and store separation systems, the aerodynamic of multi-body interaction flow field and the separation problems have been paid great attention by researchers, since they are directly related to the success of the mission. With high capital cost and technology risk of both flight and ground test, CFD technology has been more and more applied to resolve these problems for the rapid development of computer hardware resources. The accurate simulation of aerodynamic interactions and separating characters of a multi-body flow field with high Ma number continue to be one of the more challenging problems. This is mainly due to the inherent high unsteady and complex turbulent character of the transient flow field. This paper adopts overset grids to implement CFD analysis of these problems. Developments in strategies and software tools for overset structured grid generation are summarized firstly. The general principle and key technology of overset grids are followed. In the third part, one validation, store release of wing-pylon-store model, is implemented. Finally, stage separation of a Two-Stage-To-Orbit (TSTO) model is studied further to discuss hard predictable flow phenomenon and real physical mechanism of it.