ABSTRACTResearch on new techniques of side-inlet/outlet mufflers equipped with internal non-perforated intruding tubes has been discussed in recent literature; however, the research work of multi-chamber sideinlet/outlet mufflers in conjunction with cross-flow tubes and open-ended perforated intruding tubes which may efficiently increase the acoustical performance is rare. Therefore, the main purpose of this paper is not only to analyze the sound transmission loss (STL) of three kinds of side-inlet/outlet mufflers (a three-chamber muffler with cross-flow tubes, a five-chamber muffler with cross-flow tubes and a nonperforated tube, and a five-chamber muffler with cross-flow tubes and a perforated tube) but also to optimize their best design shape within a limited space.In this paper, both the generalized decoupling technique and plane wave theory in solving the coupled acoustical problem are used. A four-pole system matrix in evaluating the acoustic performance is also deduced in conjunction with a simulated algorithm (SA). A numerical case in finding the optimalSTLof mufflers, which is constrained within a basement with a side-inlet/outlet, at targeted tones has been introduced. Before the optimization is carried out, an accuracy check of the mathematical model is performed. Results reveal that the maximalSTLis precisely located at the desired target tone. Moreover, it has been seen that mufflers with more chambers will increase the acoustic performance for both pure tone and broadband noise. Additionally, the acoustical performance of mufflers conjugated with perforated intruding tubes is superior to those equipped with non-perforated tubes.Consequently, the approach used for seeking the optimal design of theSTLproposed in this study is indeed easy and quite effective.