The production of contrasted polymer-coated cardboards is necessary to establish the structure/properties relationships and produce the « just necessary » packaging materials. For that purpose, the impact of the processing parameters on the resulting structure of polymer-coated cardboards was modeled using a statistical Design of Experiment (DOE) approach. Five independent factors were considered: three numeric continuous factors, the pressure, the temperature, and the duration of thermocompression, one numeric discrete factor, the initial polymer film thickness, and one categorical factor, the cardboard type. Four responses were considered: the thicknesses of each of the three layers constituting polymer-coated cardboards (i.e., the free polymer, the impregnated, and the free cardboard) and the material’s curvature. The choice of the adequate DOE was first assessed using a Scoping Design and coupled with the characterization of the used polymer, i.e., poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV). The I-optimal DOE was found to be the most suitable and was therefore implemented. To validate the model, the DOE was then used to produce two targeted structures, one with no impregnation of the polymer and another one with a complete impregnation of the cardboard. The values of thicknesses and curvature were not significantly different from the model predictions, therefore verifying the model.