Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising strategy for selected patients with refractory cardiac arrest, improving survival and the likelihood of favorable neurological outcomes. However, neurological prognostication in this setting remains highly challenging and insufficiently standardized. The pathophysiological complexity of ECPR, including global ischemia–reperfusion injury, altered cerebral perfusion, systemic inflammation, anticoagulation and prolonged sedation, limits the reliability of conventional post-cardiac arrest prognostic tools. This narrative review provides a focused and clinically oriented synthesis of current evidence on brain injury and neuroprognostication in patients undergoing veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiac arrest. Key determinants of neurological outcome across pre-ECMO and peri-resuscitation phases are examined, alongside the role and limitations of multimodal monitoring strategies, including neurological examination, electroencephalography, neuroimaging, cerebral oximetry and circulating biomarkers. Particular attention is given to the timing of prognostication and the risk of premature or inaccurate predictions leading to self-fulfilling prophecies. Emerging data suggest that neurological recovery in ECPR patients may be delayed, supporting a more cautious and time-adapted approach. A pragmatic, multimodal framework for neurological assessment in this population is outlined. By addressing current gaps and proposing a structured approach, this review aims to inform clinical decision making and contribute to improved neurologically meaningful survival in ECPR-treated cardiac arrest.