In this research, an efficient thermal-stress coupling design method for a Chiplet-based system with a coaxial through silicon via (CTSV) array is developed by combining the support vector machine (SVM) model and particle swarm optimization algorithm with linear decreasing inertia weight (PSO-LDIW). The complex and irregular relationship between the structural parameters and critical indexes is analyzed by finite element simulation. According to the simulation data, the SVM model is adopted to characterize the relationship between structural parameters and critical indexes of the CTSV array. Based on the desired critical indexes of the CTSV array, the multi-objective evaluation function is established. Afterwards, the structural parameters of the CTSV array are optimized through the PSO-LDIW algorithm. Finally, the effectiveness of the developed method is verified by the finite element simulation. The simulated peak temperature, peak stress of the Chiplet-based system, and peak stress of the copper column (306.16 K, 28.48 MPa, and 25.76 MPa) well agree with the desired targets (310 K, 30 MPa, and 25 MPa). Therefore, the developed thermal-stress coupling design method can effectively design CTSV arrays for manufacturing high-performance interconnect structures applied in Chiplet-based systems.