Eosinophilic diseases comprise a heterogeneous spectrum of conditions characterized by increased eosinophil counts and tissue infiltration, ranging from organ-specific allergic disorders to systemic inflammatory, autoimmune, and hematologic diseases. Although traditionally classified according to the primary organ involved, increasing evidence indicates that eosinophilia often reflects a systemic immune dysregulation with shared pathogenic mechanisms and overlapping clinical phenotypes. This complexity challenges purely organ-based diagnostic and therapeutic approaches and underscores the need for biomarker-driven strategies. Eosinophils act as multifunctional effector cells bridging innate and adaptive immunity and contribute to tissue damage, vascular dysfunction, and thrombotic complications through the release of cytotoxic granule proteins, cytokines, and lipid mediators. In this context, circulating inflammatory and coagulation-related biomarkers provide a non-invasive window into disease activity, pathogenic pathways, and risk stratification. Peripheral blood eosinophil count remains a central marker, while markers of coagulation activation, mast cell–derived mediators, complement components, and type 2 inflammatory biomarkers capture complementary dimensions of eosinophilic inflammation. In airway diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps, integration of cytokine biology with circulating and airway biomarkers has enabled biomarker-guided selection of biologic therapies targeting interleukin (IL)-5, IL-4/IL-13, and upstream epithelial alarmins. Conversely, in systemic eosinophilic syndromes, immune-mediated diseases, and eosinophilic gastrointestinal disorders, validated serum biomarkers capable of guiding diagnosis and monitoring remain limited, highlighting important unmet clinical needs. Among currently available markers, blood eosinophil count has the clearest established clinical utility in severe eosinophilic asthma and CRSwNP, whereas tryptase, ANCA, C-reactive protein, IgG4, D-dimer, fibrinogen, ECP, and EDN provide context-dependent adjunctive or investigational information in systemic disease and EGID. This review provides an integrated overview of inflammatory serum biomarkers across eosinophilic diseases, emphasizing their role in disease phenotyping, risk assessment, and precision medicine. By bridging perspectives from internal medicine, immunology, pulmonology, rheumatology, and gastroenterology, we propose a unified, biomarker-informed framework to support individualized management across the eosinophilic disease spectrum. No single serum biomarker reliably captures tissue activity across all eosinophilic disorders; longitudinal interpretation together with clinical phenotype, treatment exposure, and organ-specific assessment is therefore essential.