Spray cooling, which has a fast thermal response and low flow rate consumption, is a common and effective thermal management approach for high power electronic systems. Typically, to improve the heat transfer coefficient (HTC) for spray cooling, the target surface wettability is decreased, promoting nucleation boiling by reducing the surface energy barrier for bubble nucleation. However, the merging of bubbles and the formation of a vapor film have limitations in further increasing the critical heat flux (CHF). Hence, maximizing both the HTC and CHF of spray cooling can be mutually exclusive on the same heated surface. This paper presented a novel design for a vapor-liquid separation structure surface. It consisted of lower micropillars that serve as the vapor separation channel. On top of that, there was an upper multi-layer copper micromesh that wicks and spreads the coolant. Additionally, nano-grass attached to the micromesh to enhance capillary force and increase the nucleation sites simultaneously. Subsequently, we calculated the forward velocity and pressure drop of the droplets passing through the copper mesh to study the effects of droplet velocity and capillary force on heat transfer performance. The results show that the forward velocity of the droplets decreases rapidly as the increase of copper mesh layers and it drops to zero when passing through the third mesh. Therefore, the capillary force generated by the copper mesh is another important factor for the atomized droplets to pass through the copper mesh and reach the target surface. We have proven that all the vapor-liquid separation structure surfaces satisfy the condition ΔPcap>ΔPpore+ΔPlocal. Hence, the synergistic effects of the micropillar, copper micromesh, and nano-grass enable a circulation process of wicking-rewetting-vapor evacuation, which improves the onset of nucleate boiling (ONB), enhances the HTC, and increases the maximum heat flux dissipated by the system. Enhanced HTC (7.94 W/cm2/K) and maximum heat flux (817 W/cm2) were achieved at 1.50 ml/s on the vapor-liquid separation structure surfaces (#200 2-layer), representing an enhancement of 79.6% and 80.0% compared with that for the flat surface and the temperature of the heated surface at the ONB maximum decreased by approximately 30.8 °C.