For ultrasonic plastic welding, the horn design has a great influence on the quality of the weld. The design requirements are more careful, especially when the welding profile is complex. There have been many results presented on the optimization of the profile for wide-like horns. However, there have not been many studies published on block-like horn, especially block-like horn with complex working surface profile. In this paper, an optimal design for a block-like horn with complex working surface profile used for welding turn signal lights on cars will be presented. The objectives are to achieve maximum vibration uniformity in the working surface. In addition, the vibration amplitude amplification and some other factors are also considered in the process of optimizing the horn design. The integration of three methods: finite element method, response surface methodology, and genetic algorithm is used as an optimization tool for the optimal design. The results show that all the selected design variables have the greatest influence on the amplitude uniformity, while the vibration amplitude amplification is most affected by the slot location. The amplitude uniformity achieved for the optimum block-like horn is 95%, while the amplitude amplification is 2.7. In addition, the frequency separation between the longitudinal frequency and the before and after frequencies are 1340 Hz and 1245 Hz, respectively. The optimal design process presented in this study can be considered as a guidance for block-like horn designs in industry with complex profiles in the working surface.