Background: Acute respiratory distress syndrome (ARDS) is a severe form of hypoxemic respiratory failure with high morbidity and mortality. Mechanical ventilation is essential for supportive care, but the heterogeneity of lung and chest wall mechanics limits the effectiveness of standardized approaches. Esophageal pressure (Pes) monitoring, as a surrogate of pleural pressure, provides insight into patient-specific physiology and may enable individualized ventilation strategies to minimize ventilator-associated lung injury (VALI).Objective: To determine whether esophageal pressure monitoring improves personalization of mechanical ventilation in patients with ARDS and heterogeneous lung–chest wall mechanics.Methods: A comprehensive PubMed search of English-language literature was conducted. Experimental, physiologic, and clinical studies addressing esophageal manometry in mechanically ventilated patients were reviewed, with emphasis on ARDS. Evidence was synthesized regarding PEEP titration, assessment of patient effort, and applications in complex scenarios such as obesity and COPD overlap. Data extraction focused on proposed physiologic targets, validation techniques, clinical outcomes, and bedside feasibility.Findings: Esophageal manometry enables partitioning of lung and chest wall mechanics, accurate estimation of transpulmonary pressure, and optimization of PEEP settings. Across studies, consistent target ranges were identified: expiratory transpulmonary pressure (Plexp) 0–2 cmH₂O, end-inspiratory transpulmonary pressure (Plinsp) ≤15–20 cmH₂O, and tidal transpulmonary pressure change (ΔPL) ≤10–12 cmH₂O. In assisted ventilation, diaphragmatic-protective thresholds included ΔPes 3–8 cmH₂O, ΔPdi 5–15 cmH₂O, and PTPes 60–150 cmH₂O·s/min. Technique requires careful balloon inflation (Vbest) and confirmation of placement using an occlusion test. Additional clinical uses include detection of intrinsic PEEP, assessment of hemodynamics via transmural pressure measurements, and monitoring of patient–ventilator synchrony. Collectively, these applications support lung- and diaphragm-protective ventilation strategies tailored to individual physiology.Conclusions: Esophageal pressure monitoring represents a promising adjunct for personalizing mechanical ventilation in ARDS, particularly in patients with altered chest wall mechanics such as obesity. Although technical expertise and proper calibration are required, this tool allows more precise adjustment of PEEP, tidal volume, and inspiratory effort. Integration of Pes monitoring into practice may help balance lung- and diaphragm-protective strategies, thereby reducing VALI and improving patient-specific outcomes.