The presence of a metal space frame (MSF) radome inevitably degrades the electromagnetic (EM) performance of the enclosed antenna, while the deformation of the radome can worsen the degradations. In this study, with the introduction of the concept of variable size member, a multidisciplinary optimisation model is proposed to implement the sizing optimisation for the members of MSF radomes to improve simultaneously the EM performance, structural performance, and self-weight simultaneously where EM analysis and structural analysis are involved. Furthermore, a method is presented to boost the efficiency of the EM performance analysis, which makes possible the optimisation of electrically large MSF radomes. A 70 m MSF radome is simulated, and the results indicate that the proposed radome design with variable size members is superior to the conventional radome design with constant size members in terms of all the optimisation objectives, especially the EM performance and self-weight. Several conclusions with guidance values are drawn based on the results.