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Abstract: Background Dense titanium (Ti) fusion cages have been commonly used in transforaminal lumbar interbody fusion. However, the stiffness mismatch between cages and adjacent bone endplates increases the risk of stress shielding and cage subsidence. Methods The current study presents a multiscale optimization approach for porous Ti fusion cage development, including microscale topology optimization based on homogenization theory that obtains a unit cell with prescribed mechanical properties, and macroscale topology optimization that determines the layout of framework structure over the porous cage while maintaining the desired stiffness. The biomechanical performance of the designed porous cage is assessed using numerical simulations of fusion surgery. selective laser melting is employed to assists with fabricating the designed porous structure and porous cage. Results The simulations demonstrate that the designed porous cage increases the strain energy density of bone grafts and decreases the peak stress on bone endplates. The mechanical and morphological discrepancies between the as-designed and fabricated porous structures are also described. Conclusion From the perspective of biomechanics, it is demonstrated that the designed porous cage contributes to reducing the risk of stress shielding and cage subsidence. The optimization of processing parameters and post-treatments are required to fabricate the designed porous cage. The present multiscale optimization approach can be extended to the development of cages with other shapes or materials and further types of orthopedic implants.