Background: Although rarely performed, sternal resection for chondrosarcoma presents considerable anesthetic challenges, particularly in both immediate and long-term pain management. Method: This case study details the anesthetic protocol adopted for a 61-year-old male who underwent a sternal resection, chest wall reconstruction and muscle flap coverage due to chondrosarcoma. To optimize perioperative analgesia, a thoracic epidural catheter was placed preoperatively, combined intraoperatively with bilateral parasternal blocks targeting intercostal nerves at the resection margin. General anesthesia was tailored and paired with fluid restriction and minimal vasopressor doses to stabilize hemodynamics. Result: Postoperative recovery was marked by minimal discomfort, no need for systemic opioids, and early initiation of physiotherapy. At 12 months post-surgery, the absence of persistent pain or physical dysfunction suggested that the synergistic use of thoracic epidural and parasternal blocks offers effective control over both short-term and chronic pain following major chest wall surgery. The holistic integration of psychological support and an active rehabilitation regimen exemplified a biopsychosocial strategy, instrumental to the patient’s positive trajectory. Conclusions: This experience underscores the advantage of supplementing epidural anesthesia with parasternal nerve blocks in sternal resections, facilitating better outcomes and reducing systemic opioid use. Further studies involving broader patient populations are necessary to validate and refine this promising approach in preventing chronic pain in complex thoracic surgeries.