Large defects in the congenital diaphragmatic hernia (CDH) are treated by prosthetic materials, most frequently polytetrafluoroethylene (PTFE), with high complications. The purpose of this study is to develop a novel electrospun double-faced prosthesis that will minimize these surgical complications. Polyamide 6 (PA-6) and thermoplastic polyurethane (TPU) nanofibers were prepared by solution electrospinning, and room temperature vulcanized silicone (RTV) was used in electrospinning by dip-coating to develop a double-faced membrane. The results demonstrate that the duration of electrospinning and thickness of silicone layers influence the morphology of the bilayer scaffolds. Electrospun bilayer polyamide 6/silicone and thermoplastic polyurethane/silicone scaffolds are fabricated as potential substitutes for prosthetic membrane applications in this study. The morphology, topography, mechanical, and biological properties of these electrospun meshes have been reported to make adequate conclusions in in vitro studies. The morphological characterizations show two distinct layers of electrospun and silicone layer which can mimic the morphology of PTFE prosthesis. However, the mechanical results of the developed TPU/Silicone membrane demonstrate improved mechanical properties. In addition, the biological tests confirm the biocompatibility of the developed prosthesis.