Post-cardiac arrest syndrome (PCAS) presents a multifaceted challenge in clinical practice, characterized by severe neurological injury and high mortality rates despite advancements in management strategies. One of the important critical aspects of PCAS is post-arrest lung injury (PALI), which significantly contributes to poor outcomes. PALI arises from a complex interplay of pathophysiological mechanisms, including trauma from chest compressions, pulmonary ischemia-reperfusion (IR) injury, aspiration, and systemic inflammation. Despite its clinical significance, the pathophysiology of PALI remains incompletely understood, necessitating further investigation to optimize therapeutic approaches. This review comprehensively examines the existing literature to elucidate the epidemiology, pathophysiology, and therapeutic strategies for PALI. A comprehensive literature search was conducted to identify preclinical and clinical studies investigating PALI. Data from these studies were synthesized to provide a comprehensive overview of PALI and its management. Epidemiological studies have highlighted the substantial prevalence of PALI in post-cardiac arrest patients, with up to 50% of survivors experiencing acute lung injury. Diagnostic imaging modalities, including chest X-rays, computed tomography, and lung ultrasound, play a crucial role in identifying PALI and assessing its severity. Pathophysiologically, PALI encompasses a spectrum of factors, including chest compression-related trauma, pulmonary IR injury, aspiration, and systemic inflammation, which collectively contribute to lung dysfunction and poor outcomes. Therapeutically, lung-protective ventilation strategies, such as low tidal volume ventilation and optimization of positive end-expiratory pressure, have emerged as cornerstone approaches in the management of PALI. Additionally, therapeutic hypothermia and emerging therapies targeting mitochondrial dysfunction hold promise in mitigating PALI-related morbidity and mortality. PALI represents a significant clinical challenge in post-cardiac arrest care, necessitating prompt diagnosis and targeted interventions to improve outcomes. Mitochondrial-related therapies are among the novel therapeutic strategies for PALI. Further clinical research is warranted to optimize PALI management and enhance post-cardiac arrest care paradigms.