Heat pipes are passive devices crucial for thermal management in various applications. However, conventional water-based fluids can limit their heat transfer capacity, especially in cold environments where freeze protection is necessary. This study investigates the potential of MgO-Al2O3 hybrid nanofluids to enhance heat transfer performance in cylindrical mesh heat pipes while addressing these limitations. The research demonstrates significant improvements in thermal performance compared to a water-ethylene glycol mixture. The MgO-Al2O3 hybrid nanofluid reduces thermal resistance by enhancing surface wettability in the evaporator section. Additionally, the formation of a nanofluid coating on the evaporator surface leads to a higher heat transfer coefficient. Furthermore, RSM successfully models the relationship between nanoparticle concentration, power input, and key thermal responses (thermal resistance and heat transfer coefficient). These findings highlight the effectiveness of MgO-Al2O3 hybrid nanofluids for augmenting heat transfer in heat pipes and provide valuable RSM models for predicting thermal behavior within the investigated range.