Postoperative pain, cognitive decline, and mental health issues continue to represent significant challenges following cardiac surgery. In addition to baseline morbidity and local and systemic responses to surgical trauma, perioperative emotional and psychological stressors are exceptional for cardiac surgery patients. Human beings connect emotions with their heart. Nevertheless, there is a paucity of data and guidance on innovative approaches to improving the outcomes of patients who have undergone cardiac surgery. This review will focus on the available evidence of ketamine’s potential to advance the perioperative and long-term therapy of cardiac surgery patients in a multicomponent framework as a future prospect. We will put forth a combination therapy comprising ketamine-mediated hypnotherapy as a mind–body-based approach, behavioral psychotherapy, and neurocognitive training with the use of virtual reality (VR) to augment interventions.