Electrospun scaffolds based on hydrophobic and biodegradable polymers exhibit good mechanical properties but are not suitable for cell attachment. In contrast, scaffolds with natural polymers show inherent tendency for cell attachment, but they are mechanically brittle. Thus core-shell nanostructured scaffolds are expected to be the best candidate. In the present work, attempts have been made to design and fabricate nonwoven mat based on nanofibers with core-shell structure comprising themoplastic urethane elastomer (TPU) and gelatin as core and shell respectively. For this purpose, electrospun process was employed with a core-shell type needle, and the two polymers were processed in the form of solution in several solvent. We’ve tried to use many solvents such as: DMF, DMAC, DCM, THF, HFIP and their mixture for TPU and TFA, TFE, AA, FA, DMF, HFIP and their mixture for Gt, but just HFIP as a solvent for two solutions, lead to produce core- shell structure. Effects of solution and processing parameters upon the developed nanofibers and corresponding mat micro morphology were investigated. Transmission electron microscopy (TEM) and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) evidenced the formation of the gelatin layer on the TPU fiber as the core. The bulk mechanical properties of the obtained mat was evaluated and correlated with the diameter and orientation of the core-shell nanofibers. The surface of the prepared mat exhibited a good hydrophilic behavior with excellent surface softness in the presence of an aqueous media, indicating the potential for the preparation of scaffolds with desired bulk mechanical strength as well as biocompatibility for mussel and tendon regeneration.