To obtain a better transmitter layout and enable the system to achieve higher positioning accuracy, we propose an iGPS transmitter layout optimization method based on an immune optimization algorithm. According to the system's measurement principle, we obtain the measurement uncertainty model of the system. Besides, we establish the affinity function and utilize the immune optimization algorithm for optimizing the transmitter layout. Finally, we verify the results through the simulation. The simulation analysis shows that the proposed method can significantly optimize the transmitter layout and improve the system's measurement accuracy. Thus, the immune optimization algorithm has a better global optimization effect than the genetic algorithm and can obtain better placement of transmitters.