Heart failure is the final outcome of most cardiovascular diseases and shares risk factors with other cardiovascular pathologies. Among these, inflammation plays a central role in disease progression and myocardial remodeling. Over the past 2 decades, numerous studies have explored immune-related mechanisms in cardiovascular disease, highlighting the importance of immune cross-talk between the heart and extra-cardiac organs, including bone marrow, spleen, liver, gut, and adipose tissue. This review examines how immune interactions among these organs contribute to heart failure pathogenesis, with a focus on clonal hematopoiesis, an age-related alteration of hematopoietic stem cells that fosters pathological bone marrow-heart communication. Additionally, we explore recent advances in the understanding of clonal hematopoiesis and its role in heart failure, emphasizing its implications for prognosis and potential therapeutic interventions. By integrating insights from immunology, metabolism, and aging, we provide a comprehensive perspective on the immunologic determinants of heart failure, paving the way for precision medicine approaches aimed at mitigating cardiovascular risk.