<p>Intestinal fatty acid–binding protein (I-FABP) has gained attention as a biomarker of gut epithelial injury in heart failure (HF), a condition increasingly recognized as involving multisystem dysfunction. This review synthesizes current evidence on I-FABP’s role in HF pathophysiology, prognosis, and its potential therapeutic relevance. Elevated I-FABP levels have been consistently linked with worse clinical outcomes across diverse HF presentations, including acute decompensated HF, cardiogenic shock, chronic HF, and HF following myocardial infarction. In these contexts, I-FABP reflects intestinal injury caused by splanchnic hypoperfusion or venous congestion, providing prognostic insight beyond traditional cardiac markers. In chronic HF, I-FABP correlates with gut microbiota alterations and reduced microbial diversity, supporting its role in gut barrier dysfunction and systemic inflammation through the gut-heart axis. Compared with other fatty acid–binding proteins, such as H-FABP (myocardial injury), L-FABP (hepatic and renal stress), and A-FABP (metabolic inflammation), I-FABP captures a distinct and clinically relevant dimension of HF-related organ involvement. Thus, I-FABP shows a strong potential as a multimodal biomarker for risk stratification, disease monitoring, and possibly guiding novel gut-targeted therapies in HF. Further research is warranted to validate its clinical utility and explore its integration into routine HF management.</p>