The rapid development of nuclear power plants (NPPs) in China has caused increasing attention to be paid to the treatment of low-level radioactive wastewaters (LLRWs). One possibility is the application of vacuum membrane distillation (VMD). In this study, a commercial hydrophobic microporous polypropylene membrane was investigated with respect to nuclide decontamination and permeate flux performance in the VMD process. The results demonstrate that vacuum pressure has the most obvious influence on permeate flux, followed by feed temperature and feed velocity. Despite the influence of operational parameters, effective nuclide filtering can be achieved with average decontamination factor (DF) values consistently higher than 1700. The salt concentration in the feed solution decreases the permeate flux and nuclide filtering. However, the VMD process still offers high average DF values of 6000 for Cs(I), 3700 for Sr(II), and 8300 for Co(II), even when the feed salt concentration reaches 80 g L−1. After operation at a high salt concentration, there is no obvious variation in the chemical composition on the membrane surface based on the attenuated total reflectance–Fourier transform infrared spectra. A brief comparison shows that the process integrating reverse osmosis and VMD is a promising method for treating LLRWs and minimizing radioactive waste in NPPs.