We used topology optimization technology to explore the new theory and method of interbody fusion cage design and realized an innovative design of interbody cages.The lumbar spine of a normal healthy volunteer was scanned to perform reverse modeling. Based on the scan data for the L1-L2 segments of the lumbar spine, a 3D model was reconstructed to obtain the complete simulation model of the L1-L2 segment. The boundary inversion method was used to obtain approximately isotropic material parameters that can effectively characterize the mechanical behavior of vertebrae, thereby reducing the computational complexity. The topology description function was used to model the clinically used traditional fusion cage to obtain Cage A. The moving morphable void-based topology optimization method was used for the integrated design of size, shape, and topology to obtain the optimized fusion cage, Cage B.The volume fraction of the bone graft window in Cage B was 74.02%, which was 60.67% higher than that (46.07%) in Cage A. Additionally, the structural strain energy in the design domain of Cage B was 1.48 mJ, which was lower than that of Cage A (satisfying the constraints). The maximum stress in the design domain of Cage B was 5.336 Mpa, which was 35.6% lower than that (8.286 Mpa) of Cage A. In addition, the surface stress distribution of Cage B was more uniform than that of Cage A.This study proposed a new innovative design method for interbody fusion cages, which not only provides new insights into the innovative design of interbody fusion cages but may also guide the customized design of interbody fusion cages in different pathological environments.Copyright © 2023 Elsevier Inc. All rights reserved.