High flux membranes are required for energy-efficient separation processes. Chemical treatments of conventionally prepared polyamide thin film composite (TFC) membranes, including alkali hydrolysis of polyamide, have been found suitable for achieving higher membrane permeance without significant loss in solute rejection. However, polyamide-based membranes are known to be stable in alkaline conditions during chemical cleaning. Hence, we revisited the possibility of alkali hydrolysis post-treatment of the polyamide layer of a commercial nanofiltration membrane upon short-term exposures at a wide range of pH exceeding the recommended value (up to pH 13). We optimized the post-treatment parameters using the Box Behnken design (BBD) of Response Surface Methodology (RSM) to achieve maximum pure water permeance. We observed that the pure water permeance (PWP) of the post-treated (optimum) membrane increased to 21.1 ± 0.4 LMH/bar from 12.3 ± 0.4 LMH/bar of the pristine membrane while retaining the same salt rejection. However, the chemical composition, thickness, surface charge, and pore size of the polyamide layer in the pristine and post-treated membranes were found identical. Hence, it was concluded that the increase in PWP might be attributed to the physical restructuring of the polyamide layer or restructuring of the support layer and interface, making the membrane more permeable, rather than hydrolysis of the polyamide layer.