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As therapeutic options expand, including biologic agents, there is an increasing need for biomarkers that can inform clinical decision-making and support treat-to-target strategies. This narrative review synthesizes current evidence on tissue-based, circulating, and minimally invasive biomarkers in EoE and proposes a compartment-based clinical hierarchy to contextualize their performance in routine practice. While type 2 cytokine pathways define disease biology, their systemic measurement demonstrates limited diagnostic and monitoring value. By contrast, tissue transcriptomic signatures and esophageal-proximal assessments\u2014particularly eotaxin-3 and eosinophil-derived granule proteins\u2014show stronger correlation with mucosal inflammation and therapeutic response. Structural and epithelial markers further highlight that histologic remission does not necessarily equate to restoration of mucosal integrity. 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