Acute hypoxemic respiratory failure (AHRF), particularly acute respiratory distress syndrome (ARDS), is characterized by marked heterogeneity in lung morphology and mechanics, requiring individualized mechanical ventilation strategies that balance adequate gas exchange with the prevention of ventilator-induced lung injury (VILI). Lung ultrasound (LUS) has become a cornerstone of critical care imaging, allowing differential diagnosis, quantitative assessment of lung aeration, phenotyping of ARDS morphology, and monitoring of disease evolution and complications. However, imaging alone does not provide direct guidance for optimizing ventilator settings. Some modern ventilators enable the rapid bedside acquisition of tidal pressure–volume (PV) loops, allowing tidal hysteresis to be measured and thereby providing complementary physiological information by identifying cyclic opening and closing of lung units and signs of overdistension. Emerging evidence supports the use of tidal hysteresis thresholds to identify insufficient positive end-expiratory pressure (PEEP) associated with tidal recruitment/derecruitment and to guide individualized PEEP titration during decremental PEEP trials. This review discusses the rationale and practical implementation of an integrated approach combining critical care ultrasound and PV loops throughout the management of mechanically ventilated patients with AHRF. We describe how ultrasound can support diagnosis, phenotyping, monitoring of lung aeration, and detection of ventilation-related complications, while PV loops provide a practical physiological framework for optimizing ventilator settings. This approach may provide a comprehensive, non-invasive, and repeatable bedside assessment of lung morphology, aeration, and respiratory mechanics, potentially facilitating personalized mechanical ventilation strategies aimed at reducing the risk of VILI and optimizing patient management.