This work investigated the influence of a new polymeric blend of polysulfone/polyacrylonitrile (PSf/PAN) nanofibers prepared via the electrospinning process as substrate to produce thin film composite forward osmosis (TFC-FO) membrane. The solvents in the electrospinning process were optimized. A polyamide (PA) thin layer was successfully fabricated on the electrospun nanofibrous substrate via interfacial polymerization. The performance of the nanofiber-based thin film composite (NTFC) membranes was compared with the in-house-made (PSf/PAN) TFC membrane, in which its substrate was fabricated by phase inversion. The NTFC membrane demonstrated significant improvement in hydrophilicity and water permeability, and the reverse salt flux (RSF) was reduced. In addition, the structural parameter (S) value of the fabricated NTFC decreased considerably which represented the reduction of internal concentration polarization (ICP) during the FO process. These achieved results were due to nanofiber structural characteristics such as high porosity and interconnected open pore structure. The effects of different salts as draw solutions (NaCl, KCl, MgCl2, MgSO4) on the osmotic performance of the NTFC and TFC membranes were evaluated. Among the tested draw solutions with the same osmotic pressure, the NTFC membrane exhibited higher water flux (38.3 LMH) than that of the TFC membrane (14.3 LMH) for KCl draw solution.