Trans-medium flight vehicle can obtain an attack superiority in the modern combat owing to its air/underwater cross-domain advantages. In this paper, a Fluid-Structure Interaction model of a trans-medium flight vehicle under wave conditions is established. The cavitation evolution, hydrodynamic, and trajectory characteristics of the flight vehicle under a sea condition are then studied using numerical simulation methods. The research results show that the trajectory of the trans-medium flight vehicle changes greatly during the process of wave penetration. The trans-medium flight vehicle goes through three stages, i.e., entry, immersion, and emergence. After entering the water, a deflection torque is generated via the uneven force acting on the upper and lower edges of the head and both sides of the tail, which results in a 240% change in pitch angle. Meanwhile, a 17% velocity loss occurs during touching the sea wave. The Fluid-Structure Interaction models offer valuable assistance in the design of trans-medium flight vehicle. And the analysis results indicate that the head and tail configurations need to be carefully designed to reduce the trajectory deflection and energy loss in future work.