Deep vein thrombosis (DVT) is a major contributor to cardiovascular morbidity and mortality and may arise secondary to anatomical abnormalities such as May-Thurner syndrome (MTS). We present the case of an 88-year-old female with multiple comorbidities who presented with acute left lower extremity swelling and pain following recent air travel. Imaging confirmed extensive thrombosis extending from the popliteal to the common iliac vein, with significant venous compression consistent with MTS. The patient underwent successful mechanical thrombectomy, balloon angioplasty, and venous stent placement, resulting in restoration of venous flow without immediate complications. This case highlights the importance of rapid diagnosis and intervention in extensive iliofemoral DVT and underscores the potential for delayed clinical recognition of MTS in elderly patients. Earlier recognition of underlying anatomical risk factors may improve outcomes, guide procedural planning, and help prevent recurrent thrombotic complications in high-risk populations.