<p>A precise understanding of thermal conductivity is crucial for optimizing industrial and engineering processes, which has led to increasing interest in the development of advanced fluids with enhanced thermophysical properties. In this study, the thermal performance of two ternary hybrid nanofluids MWCNT (45)-CuO (45)-SiO₂ (10)/water (90)-EG (10) (Sample A) and MWCNT (10)-CuO (45)-SiO₂ (45)/water (50)-EG (50) (Sample B) was experimentally and statistically investigated under various laboratory conditions (temperature: 30–50&#xa0;°C; volume fraction: 0.05–1.25%). Two different synthesis routes were employed to obtain ternary hybrid nanofluids with distinct compositional ratios. The crystalline structure and morphological characteristics of the nanoparticles were examined using X-ray diffraction (XRD) and scanning electron microscopy (SEM). A magnetic stirrer was also utilized during sample preparation to enhance stability and homogeneity. The results revealed that Sample A exhibited a significantly higher thermal conductivity enhancement (TCE) compared with Sample B under identical conditions. The maximum TCE reached 37.6% for Sample A, whereas Sample B showed a maximum increase of 19.3%. In addition to the experimental investigation, response surface methodology (RSM) was applied to develop a predictive correlation for thermal conductivity. The resulting model demonstrated excellent accuracy, with an R² value of 0.9984 and a mean deviation range of − 1% &lt; MOD &lt; 0.7%. Overall, the findings highlight the potential of optimally formulated ternary hybrid nanofluids to substantially improve heat transfer performance in advanced thermal management applications.</p>