The escalating incidence of heart failure globally, and in the United States, necessitates innovative solutions beyond conventional human cardiac transplantation due to donor heart shortage. Recent measures to overcome this shortage include the novel idea of cardiac xenotransplantation, with the first procedure done in January 2022 at the University of Maryland. However, the patient did not survive in the postoperative phase, highlighting potential challenges in cardiac xenotransplantation. Trace amounts of research exist on the physiological impacts subsequent to innate anatomical differences of porcine hearts, regardless of genetic modifications in growth rates. As such, this review aims to explore and address the critical implications of utilizing genetically modified porcine hearts for cardiac xenotransplantation as it pertains to postoperative physiological function. An analysis of literature discussing multiple anatomical and physiological factors, such as differences in organ dimensions, vasculature, and cardiac conduction, was carried out. Although xenotransplantation offers a promising solution, the present analysis of relevant literature points out potentially important considerations relating to long-term survivability.