Intensive care unit-acquired weakness (ICU-AW) is a common and severe complication in critically ill patients, characterized by widespread muscle weakness. The physiopathology of ICU-AW involves multiple factors, including systemic inflammation, prolonged immobilization, and the use of sedatives and neuromuscular blockers, leading to muscle atrophy and neuromuscular dysfunction. This condition significantly impacts the weaning process, as the weakened respiratory muscles and overall reduced strength contribute to difficulties in breathing spontaneously, increasing the risk of extubation failure. The presence of ICU-AW prolongs the duration of mechanical ventilation, as patients struggle to meet the necessary respiratory demands during weaning trials. Consequently, extubation may be delayed, leading to further complications such as ventilator-associated pneumonia and increased mortality. To improve weaning outcomes in patients with ICU-AW, early mobilization and physical rehabilitation are crucial. These strategies help maintain muscle strength and function, enhancing the patient’s ability to breathe independently. Additionally, tailored weaning protocols that consider the patient’s neuromuscular status, along with gradual reduction of ventilatory support, can facilitate a smoother transition from mechanical ventilation to spontaneous breathing, ultimately reducing the risk of extubation failure.