This study introduces a novel Topological Derivative-based Sensitivity Analysis (TDSA) methodology for three-dimensional (3D) discrete variable topology optimization. Recently, the authors pointed out that the discrete variable sensitivity can be related to the topological derivative, and thus can be rationally approximated by the specially customized topological derivative for plane stress problems. However, the 3D discrete variable sensitivity requires the 3D topological derivative with element-shaped (e.g., unit cube) domain perturbation, whose analytical solution is not available in the literature. This paper proposes a unified parameter fitting framework to calculate the 3D topological derivative with arbitrary shape 3D domain perturbation. The formula for spherical hole perturbation obtained through this parameter fitting framework is identical to the well-known analytical topological derivative formula. Further, the 3D discrete variable sensitivity can be easily obtained through element-shaped domain perturbation. With the recently proposed Sequential Approximate Integer Programming (SAIP), numerical examples demonstrate that TDSA is precise not only for the self-adjoint 3D minimum compliance problems but also for the non-adjoint 3D compliant mechanism design problems. In sum, numerical examples have been conducted by feeding the derived sensitivity to the SAIP optimization algorithms, and the correctness of the sensitivity information has been well demonstrated. This research further solidifies the foundation of rational discrete variable sensitivity analysis in 3D topology optimization.