Current research on sensor array layout in magnetic positioning systems primarily focuses on quantity and spacing. In related research, the sensor array layout is typically evenly distributed, with limited investigation into the impact of spatial design on system positioning accuracy. Addressing the non-uniform distribution of sensor arrays in magnetic localization systems, this paper proposes an optimization method combining genetic algorithms with finite element simulations. This method determines the optimal sensor layout based on specific trajectories of magnetic targets. Firstly, a simulation model was established for numerical simulation of the magnetic positioning process, and the sensor array layout corresponding to the motion trajectory of each target was optimized by genetic algorithms. Secondly, based on the simulation optimization, an experimental platform for magnetic positioning systems with adjustable sensor installation positions was designed and constructed. Finally, comparative experiments were conducted on five specific magnetic target trajectories using both uniformly distributed and optimized non-uniformly distributed sensor layouts. For example, under trajectory five, the average positioning error of the optimized layout is reduced by 14.3% compared to the pre-optimization layout, and the average orientation error is reduced by 16.3%. The results indicate that uniformly distributed sensor array is not the optimal layout, and optimizing sensor array layout can effectively improve system localization and orientation accuracy.