In this study, because the use of semicrystalline polypropylene (upper material) leads to the scattering of laser radiation, an integrated method for a numerical-simulation-driven optimization of the laser transmission welding (LTW) process was investigated through the finite element method (FEM), response surface methodology (RSM), and experiments (EX). First, EX for measuring the actual laser power and spot diameter within the weld interface were conducted; these were used to simulate the temperature field and molten pool geometric characteristic parameters of the LTW process. Then, central composite design was used to design the EX, and RSM was used to establish mathematical models. Finally, the desirability function was used to determine the optimal process parameters. The experimental results nearly agreed with the simulated and predicted values. The results illustrate that the integrated (FEM–RSM–EX) approach was an effective optimization method and could play a significant guiding role in LTW EX and in quickly optimizing the process parameters. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40396.