Fully Ceramic Microencapsulated (FCM) fuel is a new type of material in nuclear energy field. It has become a promising accident tolerant fuel (ATF) candidate due to its advantages of high radiation stability, high fission product containment capacity and excellent thermo-mechanical performance. During operation, the temperature, stress, deformation and other key parameters will change significantly, which directly affect the safety of nuclear reactor. Therefore, it is necessary to carry out a multi-physics fully-coupled analysis suitable for the multi-scale, multi-component, multi-phase and nonlinear coupling processes in the reactor, so as to sort out the influences of material properties, radiation behavior, thermo-mechanical performance from numerous influencing factors. In this paper, based on the irradiation-thermo-mechanical coupling method, the performance of TRISO-based FCM fuel under irradiation conditions was analyzed, key thermo-mechanical parameters and other influencing factors of the fuel were obtained, failure behavior of the fuel element was evaluated. On this basis, the theoretical and numerical model of multi-objective optimization method were established, the optimum parameters including material properties, fuel geometry and particle arrangement were found by optimization method. The optimization results showed that the multi-objective optimization results could provide multiple Pareto optimal solutions for the FCM fuel. Specifically, when the TRISO particle spacing is 200 µm and 150 µm, the objective function difference between the optimal heat transfer solutions is only about 1.7%, meanwhile the mechanical properties vary significantly (the difference between the objective functions of the optimal solutions is about 12.4% ∼26.5%), indicating the response of stress is more sensitive than temperature. When the TRISO particles are tightly packed (particle spacing less than 100 µm), the difference of objective function between the optimal solutions is less than 5%, illustrating the optimization has limited improvement on the thermo-mechanical performance of the fuel, namely the optimization space is limited.