A design indicators prediction model using the Bell-Delaware method for a shell-and-tube heat exchanger with segmental baffles (STHX-SB) is constructed and validated by experiment. The average errors of heat transfer capacity and tube-side pressure drop are 8.52% and 7.92%, respectively, and the predicted weight is the same as the weight obtained by Solidworks commercial software, which indicates the model’s reliability. Parametric influences of the outside diameter of the heat dissipation tube, clearance between heat dissipation tubes, heat dissipation tube length, and tube bundle bypass flow clearance on heat transfer capacity per tube-side pressure drop and heat transfer capacity per weight are studied, and it indicates that whether the interaction between factors is considered or not, both heat transfer capacity per tube-side pressure drop and heat transfer capacity per weight are the most sensitive to outside diameter of heat dissipation tube and the least sensitive to heat dissipation tube length based on the Sobol’ method. To avoid falling into local optima due to algorithm convergence being too fast and to improve the reliability of solving complex optimization problems, Non-Dominated Sorted Genetic Algorithm II (NSGAII) and Multi-Objective Particle Swarm Optimization (MOPSO) embedded grouping cooperative coevolution (NSGAII-MOPSO-GCC) is proposed to optimize the studied four configuration parameters to maximize heat transfer capacity per tube-side pressure drop and heat transfer capacity per weight for STHX-SB, simultaneously. Compared with the original structure, heat transfer capacity per tube-side pressure drop and heat transfer capacity per weight of the chosen solutions separately increased by 57.66% and 4.63%, averagely, and in the optimization comparison of NSGAII, MOPSO, and NSGAII-MOPSO-GCC, NSGAII-MOPSO-GCC has the best performance, which shows that the proposed method is effective and feasible and can supply beneficial solutions and valuable guidance for heat exchanger design and improvement.