Heart failure remains the leading cause of death in many industrialized nations owing to the inability of the myocardial tissue to regenerate. The main objective of this work was to develop a cardiac patch that is biocompatible and matches the mechanical properties of the heart muscle for myocardial infarction. The present study was to fabricate poly (glycerol sebacate)/gelatin (PGS/gelatin) core/shell fibers and gelatin fibers alone by electrospinning for cardiac tissue engineering. PGS/gelatin core/shell fibers, PGS used as a core polymer to impart the mechanical properties and gelatin as a shell material to achieve favorable cell adhesion and proliferation. These core/shell fibers were characterized by scanning electron microscopy, contact angle, Fourier transform infrared spectroscopy, and tensile testing. The cell-scaffold interactions were analyzed by cell proliferation, confocal analysis for the expression of marker proteins like actinin, troponin-T, and platelet endothelial cell adhesion molecule, and scanning electron microscopy to analyze cell morphology. Dual immunofluorescent staining was performed to further confirm the cardiogenic differentiation of mesenchymal stem cells by employing mesenchymal stem cell-specific marker protein CD 105 and cardiac-specific marker protein actinin. The results observed that PGS/gelatin core/shell fibers have good potential biocompatibility and mechanical properties for fabricating nanofibrous cardiac patch and would be a prognosticating device for the restoration of myocardium.