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Clonal hematopoiesis (CH) is increasingly recognized not only as a predisposing factor for overt hematologic malignancies but also as a contributor to cardiovascular, metabolic, and other age-associated degenerative and inflammatory disorders. These associations likely arise from complex heterotypic interactions between clonally affected and non-clonal immune cells, leading to systemic immune dysregulation and chronic inflammation that affects multiple organ systems, most prominently the cardiovascular system. Somatic mutations typically linked to myeloid neoplasms disturb the inflammatory homeostasis of hematopoietic and immune compartments, resulting in a persistently heightened inflammatory state and exaggerated responses under stress conditions. Pattern-recognition receptors (PRRs) of the innate immune system detect pathogen- or damage-associated molecular patterns and activate supramolecular organizing centers (SMOCs) and downstream signaling cascades-including the inflammasome, myddosome, trifosome, necroptosome, and the TGF-β pathway-that drive the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IFN-I, and IL-6. Recent studies have begun to elucidate the mechanisms by which CH-associated mutations confer clonal advantage and dysregulate inflammatory signaling, bridging hematologic and degenerative diseases. A better understanding of these mechanistic links may facilitate the development of targeted therapies aimed at curbing clonal evolution and mitigating inflammation-driven comorbidities. In this review, we summarize the current knowledge on CH, its impact on immune dysregulation, and emerging therapeutic opportunities.