Membrane distillation (MD) is promising for many applications such as seawater desalination. Designing membranes with high vapor flux is preferred to achieve high efficiency. However, understanding of effects of the membrane interfacial wetting properties on the vapor flux in MD is still missing. Here, elucidating this effect by theoretical and experimental tools is presented. Three interfacial wetting properties are identified, namely slip vs. non-slip, wetting vs. non-wetting and rough evaporation interface. While superhydrophobic surfaces of the membrane offer slippage of fluid, the effect of the slip condition has little effect on the heat and mass transfer in MD due to the relatively small slip length. When the fluid penetrates into and wets the membrane, the vapor flux increases due to the shortened vapor transport distance although the stagnant penetration layer hinders heat transfer. The rough evaporation interface with increased evaporation area does not necessarily significantly increase vapor flux. The rough evaporation problem can be reduced to an equivalent partial wetting problem with a certain wetting depth. This work clarifies the role of membrane interfacial wetting properties in vapor flux variation, which provides guidance for future membrane interfacial design to enhance vapor flux in MD.