Primary leiomyosarcomas of the inferior vena cava (IVC) are rare tumors with complex anatomical relationships. Surgical resection remains the primary approach for management, with selective use of preoperative radiation and chemotherapy. Given the propensity for local invasion of these tumors, radical resection of surrounding structures is often required. Herein we describe the presentation, work-up, operative management, and outcomes of these lesions through the case of a patient with a tumor involving the middle segment of the IVC. Given the extent of involvement, IVC resection with en bloc right nephrectomy, right adrenalectomy, and partial left renal vein resection was performed with vascular reconstruction using a prosthetic graft. With appropriate preoperative planning and a well-coordinated multidisciplinary approach, aggressive surgical resection can be safely performed and patients can benefit from favorable long-term survival.