Several process variables can be taken into account to optimize the fused filament fabrication (FFF) process, a promising additive manufacturing technique. To take into account the most important variables, a numerical-experimental roadmap toward the optimization of the FFF process, by taking into account some physico-chemical and mechanical characteristics, has been proposed to implement the findings through the thermal behavior of materials. A response surface methodology (RSM) was used to consider the effect of liquefier temperature, platform temperature, and print speed. RSM gave a confidence domain with a high degree of crystallinity, Young’s modulus, maximum tensile stress, and elongation at break. Applying the corresponding data from the extracted zone of optimization to the previously developed code showed that the interaction of parameters plays a vital role in the rheological characteristics, such as temperature profile of filaments during deposition. Favorable adhesion could be achieved through the deposited layers in the FFF process. The obtained findings nurture motivations for working on the challenges and bring us one step closer to the optimization objectives in the FFF process to solve the industrial challenges.