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Heart failure (HF) is a progressive, multifaceted condition characterized by complex pathophysiological mechanisms, including chronic inflammation, which contributes significantly to disease onset and progression. Despite advancements in pharmacological therapies, such as angiotensin-converting enzyme inhibitors and β-blockers, HF remains associated with high morbidity and mortality. Inflammatory cytokines have emerged as potential biomarkers for HF, offering insights into disease mechanisms, risk stratification, and therapeutic responses. However, their clinical utility is hindered by analytical variability, pre-analytical challenges, and limited reproducibility across studies.This review explores the role of inflammatory cytokines in HF, evaluating their pathogenetic significance, analytical performance, and prognostic value. Biomarkers such as TNFα, IL-6, sTNFR1, and gp130 are assessed for their ability to enhance diagnostic precision and predict adverse outcomes. Furthermore, we examine the limitations of current cytokine assays, including sample stability, diurnal variation, and lack of standardization, which affect their transition into clinical practice. While natriuretic peptides and cardiac troponins remain the gold standard for HF biomarkers, multimarker approaches incorporating inflammatory cytokines may provide a more comprehensive understanding of HF pathophysiology.The findings underscore the need for robust, standardized methodologies and novel biomarkers beyond established pathways. These efforts will enhance HF management by improving risk stratification, guiding personalized treatment strategies, and advancing our understanding of inflammatory processes in HF progression.