Management of produced water from shale gas production is a global challenge. Vacuum membrane distillation (VMD) is considered a promising solution because of its various advantages. However, low-surface-tension species in produced water can easily deposit on the membrane surface and cause severe fouling or wetting problems. To solve the problems, an omniphobic polyvinylidene difluoride (PVDF) hollow-fiber membrane has been developed via silica nanoparticle deposition followed by a Teflon AF 2400 coating in this study. The resultant membrane shows good repellency toward various liquids with different surface tensions and chemistries, including water, ethylene glycol (EG), cooking oil, and ethanol. It also exhibits stable performance in 7 h VMD tests with a feed solution containing up to 0.6 mM of sodium dodecyl sulfate (SDS). In addition, the effects of surface energy and surface morphology as well as nanoparticle size on membrane omniphobicity have been systematically investigated. This work may provide valuable guidance to molecularly design omniphobic VMD membranes for produced water treatment.