In the recent years, new methods have been devised to produce plastic parts with an increase in the use of polymers. Thermoforming, one of the most important ways, is created for production large parts with same thickness. The thermoforming process is widely used to production of packaging containers made of both thermoplastic and multi-layer sheet. Thickness distribution of thermoforming products is one of the effective parameters to characterize the produced quality. Nowadays try-and-error-based methods are utilized to predication of this parameter which are costly and time consuming. Hence, in this research the effect of different parameters including the temperature, pressure, and thermoforming method (pressure, vacuum, and integrated pressure-vacuum method) on the both thickness distribution and amount of forming of multi-layer sheets has been investigated employing design of experiment (DOE). To achieve this goal, the modular thermoforming machine has been built with the capability of forming parameter setting. The simulation has been also implemented to calculate the suitable machine clamping force to remove wrinkles created in the initial tested specimen. The results show that the integrated pressure-vacuum method has the most effect and results in increasing the thickness difference and the amount of forming as well as increase of pressure. On the other hand, the change of temperature has minimal effect of the both thickness distribution and amount of forming. Keywords: Thermoforming, Multi-layer sheet material, Modular thermoforming machine, Thickness distribution, Wrinkles, Computer simulation.