GLP-1 receptor agonists and dual GIP/GLP-1 agonists demonstrate therapeutic benefits in obesity-related heart failure with preserved ejection fraction by reducing ectopic fat deposits across multiple organs including the heart, liver, and kidneys. These incretin-based therapies improve exercise capacity, reduce congestion, and decrease heart failure events while promoting favorable cardiac remodeling through weight loss and reduced systemic inflammation. The research reframes obesity-related HFpEF as a comprehensive cardio-renal-hepatic-metabolic syndrome rather than an isolated cardiac condition. This multi-organ perspective represents a significant shift in understanding heart failure pathophysiology, particularly relevant as obesity rates climb globally and HFpEF becomes the dominant form of heart failure in aging populations. The mechanistic clarity around visceral and epicardial fat as drivers of multi-organ dysfunction provides a compelling rationale for weight-directed therapies. However, this appears to be a review synthesizing emerging data rather than presenting novel trial results. The call for future trials with multi-organ imaging endpoints suggests the field is still building evidence for optimal treatment protocols and patient selection criteria.