Particulate fouling, a typical scaling formation in heat transfer tubes, is a crucial cause of pipe clogging and thermal efficiency reduction. We innovatively proposed a new type of self-rotating rotor inserted into tubes to improve the antifouling performance and employed the Eulerian−Eulerian model incorporating an empirical fouling model that accounted for both particle deposition and removal mechanisms. Additionally, we utilized the multiple reference frame (MRF) model to simulate the rotation of the self-rotating rotor at various flow rates. To investigate the influence of the configuration parameters and optimize the thermal and antifouling performance of the self-rotating rotor, we combined the response surface method (RSM) with a multiobjective genetic algorithm (MOGA). First, we observed that the temperature increment initially increased and then decreased with increasing in velocity. Moreover, the temperature increment initially decreases and then increases with an increase in the width of the rotor, and it decreases as the pitch of the rotor increases. The fouling resistance decreases with increasing velocity, while the relationship between fouling resistance and width/pitch varies with velocity. To determine the sensitivity of the temperature increment and fouling resistance to the configuration parameters, we conducted local sensitivity analyses, demonstrating that pitch had the most significant effect on the temperature increment, followed by velocity, while width exhibited the least influence. Furthermore, the fouling resistance was found to be highly sensitive to changes in velocity with a sensitivity value of −96.01%. Based on Pareto set analysis, we identified an optimal configuration that resulted in a 9.4% enhancement in the temperature increment and a 59.3% reduction in fouling resistance. These findings can serve as valuable references for the selection and design of self-rotating rotors.