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A 3-D model of multichip module (MCM) is built with ANSYS and the temperature field distribution is studied. A regression equation describing the relationship of structure parameters and material properties with the maximum chip junction temperature of MCM is made, which integrates the response surface methodology and ANSYS. Quantitative analysis of the effect of four design parameters on the maximum chip junction temperature of MCM is studied. The four design parameters are the thickness of the substrate, thermal conductivity of the substrate, thermal conductivity of the thermal grease, and convection heat transfer coefficient, respectively. The accuracy and validity of the regression equation are validated by simulation with ANSYS. In addition, the maximum error between the calculation value of the regression equation and the simulation value with ANSYS is 0.541^\circC. With the regression equation, the thermal optimization design results of the four parameters are Ktg=5~W/m~^{\circ}C, \delta=2.5~mm, Ks=290~W/m~^{\circ}C, and h=55~W/m^2~^\circC, which lead to the maximum chip junction temperature Tjmax=89.172^{\circ}C as the minimum value. [ABSTRACT FROM AUTHOR]