With the rapid development of nanotechnology, nucleate boiling has been widely applied to the thermal management of nanoelectronics, owing to its highly-efficient heat transfer characteristics. Considering the scale effects, such as temperature jump at solid-liquid interface, a further study of nucleation boiling mechanism at a microscopic level is needed. At present, extensive studies have been carried out for providing a significant insight into the formation of nano-bubbles in a nanoscale thermal system, but the effect of heat transfer efficiency affected by the surface wettability on bubble nucleation over solid substrate is rarely available in the literature. Therefore, in this paper, the effect of surface wettability on the initial nucleation process and growth rate of bubbles are investigated and the mechanism of bubble nucleation on a nanoscale is analyzed, by the molecular dynamics simulation. The modified Lennard-Jones potential is used for investigating the solid-liquid interaction. Changing the potential parameters αand βcan obtain different surface wettability. The atomic sites, liquid density profiles and bubble nucleus volumes are computed to compare the processes of bubble nucleation on different surfaces. The variation of liquid temperature, potential and absorbed heat flux with heating time are evaluated to explore the mechanism of bubble nucleation. The simulation results show that the surface wettability influences the bubble nucleation and heat transfer at liquid-solid interface significantly. On the one hand, the bubble nucleation is promoted by properly increasing the liquid-solid interaction, which is distinctly different from the existing classical theory related to nano-bubble preferably formed on a hydrophobic surface. This is because the thermal resistance of the solid-liquid interface on a nanoscale cannot be neglected. The interface thermal resistance will decrease with the increase of wettability. Therefore, the heat transfer efficiency is higher for a stronger liquid-solid interaction so that the liquid over the hot wall obtains more energy to make bubble nucleus generated earlier. On the other hand, the surface wettability also influences the bubble growth rate. The stronger the liquid-solid interaction, the faster the bubble grows. When the volume of bubble reaches a certain value, a vapor film is formed on the substrate, leading to film boiling. Furthermore, it also illustrates that initial heat flux increases with time. In this stage, the heat flux curve shows two kinds of slopes, corresponding to the occurrence of evaporation and bubble nucleation, respectively. Then, after a certain time, the heat flux profile presents a declining trend, indicating a change into film boiling.