Nanotechnology has made biocompatible nanofibers grow in the healthcare industry. Herein, a cellulose acetate (CA) electrospun membrane was characterized by nanofibers of 438 (nm) in diameter between virus and bacteria, pore areas of 36.3%, and a pore size of 395 ± 263 (nm). This structure led to excellent air-water transfer through pore connectivity, contributing to sufficient wettability, air permeability, and water vapor transmission rate (WVTR). The air permeability of pristine CA membranes became predictable through multiple linear regression, based on the correlation to thickness, bulk density (Pearson’s coefficients: 0.754, −0.538). Nonetheless, the tensile strength of the pristine CA needed to be reinforced by spray coating with waterborne polyurethane (WPU) and graphene oxide (GO). The WPU/GO 6:1 (v/v) ratio was optimal due to the increase in ultimate tensile stress to 132.96% due to a synergy of GO’s covalent bonds with WPU’s hard segments and elongation at break to 113.40% from WPU polyols. The WPU/GO 6:1 coated CA membrane possessed still comparable air permeability (36.53 l/m2/s), and WVTR (5736 g/m2/day). Its rapid wetting transition from the Cassie-Baxter’s to Wenzel’s state was attributed to GO’s hydrophilic functional groups. These achievements in reinforcement of tensile strength and wettability would pave the way for filtration, and wound dressing.