Thoraco-abdominal aortic aneurysm (TAAA) open repair is a high-risk surgery further burdened with both mortality and morbidity. Despite numerous experimental endeavors and technical advancements, spinal cord ischemia (SCI) is still the most formidable morbidity to be resolved, irrespective of the open or endovascular surgical approach. It presents a spectrum of severity, ranging from temporary or permanent paraparesis to paraplegia with or without autonomic dysfunction. The timing of SCI occurrence is a crucial factor, with approximately 15% of cases manifesting intraoperatively, 50% within 48 h post-surgery, and the remaining 35% classified as late SCI, occurring more than 48 h after the procedure. The mechanism responsible for SCI is complex and multifactorial; hence, understanding its underlying pathophysiology is essential for its effective management. Over the last decade, strategies to enhance spinal cord perfusion and minimize the risk of SCI during TAAA open repair have been implemented. These include optimization of hemodynamics, hemoglobin levels, cardiac function, and cerebrospinal fluid pressure, ensuring collateral vascular network stability and distal aortic perfusion and intrathecal administration of drugs. A multimodal approach involving anesthesiologists and surgeons can lead to improved neurological recovery and a reduced incidence and severity of SCI.