Background: Ischemic heart disease (IHD) remains a primary cause of morbidity and mortality worldwide. Identifying effective biomarkers for early diagnosis is crucial for optimal patient outcomes. Serum Soluble Suppression of Tumorigenicity 2 (sST-2), a member of the interleukin-1 receptor family, has gained attention as a novel marker for myocardial stress and injury. Methods: This case-control study, conducted at Benha University Hospitals between February and December 2023, involved 60 IHD patients (30 with acute myocardial infarction [AMI] and 30 with angina pectoris) and 20 healthy controls. Serum sST-2 levels and traditional cardiac biomarkers (troponin I, CK, and CK-MB) were measured using ELISA. Statistical analyses were performed to assess correlations between sST-2 and various clinical parameters, including BMI, lipid profiles, blood pressure, and LVEF. Results: Serum ST-2 levels were significantly elevated in AMI (78.3 ± 37.3 ng/ml) and angina patients (71.4 ± 39.7 ng/ml) compared to controls (26.1 ± 6.9 ng/ml, P < 0.001). Troponin I and CK-MB were also higher in both patient groups versus controls (P < 0.001). Positive correlations were identified between sST-2 and BMI (r = 0.314, P = 0.005), SBP (r = 0.303, P = 0.006), and troponin I (r = 0.396, P < 0.001), while significant negative correlations were noted with LVEF (r = -0.526, P < 0.001). Conclusion: Serum sST-2 shows promise as a diagnostic and prognostic biomarker for IHD. Integrating sST-2 into clinical practice could improve the early identification and management of IHD, particularly in acute coronary syndromes.