Vacuum membrane distillation (VMD) is a promising technology for high salinity wastewater treatment. One of the key issues in VMD research is improving the antifouling performance of the hydrophobic porous membrane under proper interface modification theory and approach. In this work, the polypropylene (PP) composite membrane coated with SiO2 nanoparticles and fluorinated modification was fabricated to simultaneously enhance the interface roughness and superhydrophobicity. The fabricated superhydrophobic PP membrane was then applied to treat highly concentrated NaCl (15 wt%)/MgCl2 (from 3 to 9 wt %) saline solution in VMD process under various flow conditions. The model concerning the surface roughness and surface nucleation free energy was constructed to predict the influence of membrane surface structure on potential anti-fouling and antiwetting properties. Classical heterogeneous nucleation theory was introduced to illuminate the improved performance of developed membrane with targeted surface morphology on inhibiting the initial interfacial nucleation process. The experimental results illustrated the fabricated superhydrophobic PP membrane exhibited unique anti-fouling and anti-wetting abilities, as well as extremely stable permeating flux even under low feed rate and highly concentrated salt solution system during the continuous operation. In addition, it was also indicated that sodium ion and magnesium ion with distinct features in the structure of water-ion solution system had the potential impact on the permeate flux decline and concentration polarization effect, which was helpful for further improving the stability and durability of this series modified membrane when treating the high concentrated multiple solution system.