The present work aims at understanding the relationship between heating conditions, rheological behavior and thickness distribution that lead to the optimization of the latter in thermoforming. The materials used in this study were polystyrene, PS, high-impact polystyrene, HIPS, and a 50/50 w/w % blend of the two. The study was done by investigating computationally the influence of the material thermo-rheological properties on sheet temperature and final thickness distribution of a vacuum-produced part and relating the sheet heating conditions with the forming stage. When sheet temperature is uniform, the degree of strain hardening and the failure behavior in extension are the most important parameters in controlling the kinetics of the process and the thickness profile. In the case of nonuniform sheet temperature, the results show that an increased degree of strain-hardening is more relevant to the dynamics of the process than relatively small differences in sheet temperature. However, the solution of the inverse thermoforming problem (determining the heater temperature that induces a certain thickness distribution) showed that under practical processing conditions the effect of differences in thermal properties are predominant over the rheological ones.