In this study, we present a simple approach for developing a biocompatible polymer scaffold with a honeycomb-like micropattern. We aimed to combine a plasma treatment of fluorinated ethylene propylene (FEP) substrate with an improved phase separation technique. The plasma exposure served for modification of the polymer surface properties, such as roughness, surface chemistry, and wettability. The treated FEP substrate was applied for the growth of a honeycomb-like pattern from a solution of polymethyl methacrylate (PMMA). The properties of the pattern were strongly dependent on the conditions of plasma exposure of the FEP substrate. The physico-chemical properties of the prepared pattern, such as changes in wettability, aging, morphology, and surface chemistry, were determined. Further, we have examined the cellular response of human osteoblasts (U-2 OS) on the modified substrates. The micropattern prepared with a selected combination of surface activation and amount of PMMA for honeycomb construction showed a positive effect on U-2 OS cell adhesion and proliferation. Samples with higher PMMA content (3 and 4 g) formed more periodic hexagonal structures on the surface compared to its lower amount (1 and 2 g), which led to a significant increase in the pattern cytocompatibility compared to pristine or plasma-treated FEP.