This study presents the fabrication of double-layer electrospun nanofibrous membranes (DL-ENMs) using polyvinylidene fluoride (PVDF) and polyether sulfone (PES) based polymers with different degrees of hydrophilicity (PES, sulfonated PES, and PES with hydroxyl terminals). A comparative analysis was carried out with single-layer electrospun nanofiber membranes (SL-ENM) with a total thickness of about 375 μm. Using feed solutions, including sodium chloride, sodium nitrate, and simulated nuclear wastewater (SNWW), the performance of DL-ENMs was evaluated for desalination and radionuclide decontamination by direct contact membrane distillation (DCMD) and air gap membrane distillation (AGMD) techniques. The results showed that DL-ENMs, especially those incorporating a sulfonated PES-based hydrophilic layer, exhibited superior permeate fluxes, reaching values of 72.72 kg/m2.h and 73.27 kg/m2.h in the DCMD using aqueous feed solutions of NaCl and NaNO3, respectively, and 70.80 kg/m2.h and 41.96 kg/m2.h using aqueous feed solutions of SNWW in DCMD and AGMD, respectively. Both SL-ENMs and DL-ENMs exhibited high rejection efficiencies and decontamination factors for the feed solutions (>99.9%). In addition, the prepared ENMs were exposed to gamma radiation to evaluate their applicability in real-life applications. The result of irradiation revealed the negative impact of gamma radiation on the fluorine content of PVDF which could be a critical point in using PVDF as a hydrophobic material for decontaminating nuclear wastewater by membrane distillation.