Subsidence of interbody devices into the vertebral body might result in serious clinical problems, especially when the devices are not well designed and analyzed. Recently, some novel designs were proposed to reduce the risk of subsidence, but those designs are based on the researcher's experience. The purpose of this study was to discover the interbody device design with excellent subsidence resistance by changing the device's shape. The three-dimensional nonlinear finite element models, which consisted of the interbody device and vertebral body, were created first. Then, the simulation-based genetic algorithm, which combined the finite element model and the searching algorithm, was developed by using ANSYS® Parametric Design Language. Finally, the numerical results were carefully validated with the use of biomechanical tests. The optimum shape design obtained in this study looks like a flower with many petals and it has excellent subsidence resistance when compared with the other designs provided by the past studies. The results of the present study could help surgeons to understand the subsidence resistance of interbody devices in terms of their shapes and has directly provided the design rationales to engineers.