Objectives: Non-ST-elevation myocardial infarction (NSTEMI) is characterized by the absence of pathological ST segment elevation but an increase in biological markers. The SYNTAX II score (SS-II) is calculated to evaluate the complexity of coronary artery disease and to guide treatment decisions between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The aim of this study is to evaluate the relationship of socio-demographic data and biochemical markers with SS-II in NSTEMI patients. Materials and Methods: Six hundred patients who were admitted to the private Aktif International Hospital cardiology clinic between January 2020 and January 2024 and were diagnosed with NSTEMI were included in the study. Severity, extent, and clinical evaluation of atherosclerosis were determined using risk factors, laboratory tests, and coronary angiography. Patients were divided into two groups according to their SS-II score: low (≤ 22) and high SS-II (> 32). Socio-demographic data, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and monocyte-to-HDL-C ratio (MHR) were compared between the two groups. Results: Group 1 (SS-II ≤ 22) included 380 patients, and group 2 (SS-II > 32) included 220 patients. There was a statistically significant difference in HDL, creatine value, white blood cell, troponin I, hs-TnT, and monocyte values in group 2 compared with group 1 (p = 0.001, p = 0.018, p = 0.031, and p = 0.001, respectively). NLR, MLR, MHR, and SS values were statistically significantly higher in group 2 compared with group 1 (p = 0.015, p = 0.002, p = 0.001, and p = 0.001, respectively). The risk factors were found to be significantly associated with high-risk NSTEMI (SS-II > 32) in a logistic regression analysis and included peripheral artery disease (PAD) (OR: 3.028, p = 0.040), troponin I (OR: 3.575, p = 0.015), hs-TnT (OR: 4.221, p = 0.010), NLR (OR: 1.528, p = 0.024). MLR (OR: 5.248, p = 0.012), and MHR (OR: 7.122, p = 0.010). ROC analysis revealed that NLR (AUC: 0.691, p = 0.016), MLR (AUC: 0.731, p = 0.004), and MHR (AUC: 0.824, p = 0.003) had higher predictive power than other parameters in patients with high-risk NSTEMI (SS-II > 32). Conclusions: We found that NLR, MLR, and MHR levels are associated with the severity of coronary artery disease. We think that adding these easily and quickly measurable parameters to routine laboratory results may support the clinician in evaluating the complexity of coronary artery disease and guiding treatment decisions in NSTEMI patients.