Aptasensors have emerged as a powerful strategy for clinical diagnostics due to their enhanced specificity and selectivity in detecting biomarkers. However, striking a delicate equilibrium between sensitivity, specificity, and stability remains a formidable challenge due to the biomarker's low abundance and clinical biospecimen's complexity. To address this, we developed a hybrid of zirconia-gold nanoparticles (ZrO2-AuNPs) to enhance the performance of aptasensors, resulting in improved sensitivity and stability. The introduction of ZrO2 resulted in a significant reduction in signal fluctuation, as demonstrated by a remarkable decrease in the relative standard deviation (RSD) from 22.60% to an impressive 1.95%, indicating improved stability; this enhancement was also observed in various ZrO2-AuNPs-aptasensors, yielding a minimal RSD of 2.61%. The sensitivity boosters (ZrO2 and AuNPs) amplified the electrochemical signal, leading to highly sensitive carcinoembryonic antigen (CEA) detection with a threshold as low as 42.504 fg/mL. For clinical application, the ZrO2-AuNPs-aptasensor demonstrated a strong correlation with clinical measurements, as evidenced by the regression equation y (A) = 1.005 × x - 0.025 (ng/mL) and a notable R2 value of 0.991, indicating a high predictive accuracy. Additionally, the aptasensor displayed remarkable diagnostic accuracy in distinguishing lung cancer from healthy samples, as evidenced by a perfect sensitivity of 1.0, a specificity of 0.913, and an impressive AUC value of 0.993 in the ROC analysis, a claim further confirmed by a significantly low p-value of 1.990 × 10-5 from a validation t-test. Moreover, we optimized various conditions, including temperature and pH, for the ZrO2-AuNPs-aptasensor, resulting in desirable reproducibility and selectivity. We anticipate that the ZrO2-AuNPs strategy will enhance the aptasensor's sensitivity and stability, potentially propelling advancements in clinical diagnostics.