The machining of polymers has become widely common in several components of industry 4.0 technology, i.e., mechanical and structural components and chemical and medical instruments, due to their unique characteristics such as: being strong and light-weight with high stiffness, chemical resistance, and heat and electricity insolation. Along with their properties, there is a need to attain a higher quality surface finish of machined parts. Therefore, this research concerns an experimental and analytical study dealing with the effect of process parameters on process performance during the turning two different types of polymers: high-density polyethylene (HDPE) and unreinforced polyamide (PA6). Firstly, the machining output responses (surface roughness (Ra), material removal rate (MRR), and chip formation (λc)) are experimentally investigated by varying cutting speed (vc), feed rate (f), and depth of cut (d) using the full factorial design of experiments (FFD). The second step concerns the statistical analysis of the input parameters’ effect on the output responses based on the analysis of variance and 3D response surface plots. The last step is the application of the RSM desirability function, genetic algorithm (GA), and hybrid FFD-GA techniques to determine the optimum cutting conditions of each output response. The lowest surface roughness for HDPE was obtained at vc = 50 m/min, f = 0.01 mm/rev, and d = 1.47 mm and for PA6 it was obtained at vc = 50 m/min, f = 0.01 mm/rev, and d = 1 mm. The highest material removal rate was obtained at vc = 150 m/min, f = 0.01 mm/rev, and d = 1.5 mm for both materials. At f = 0.01 mm/rev, d = 1.5 mm, and vc = 100 for HDPE, and vc = 77 m/min for PA6, the largest chip thickness ratios were obtained. Finally, the multi-objective genetic algorithm (MOGA) methodology was used and compared.