The treatment of organic waste or wastewater with high organic solvent content has been challenging in industries as it cannot be done effectively using conventional wastewater treatment technologies such as biodegradation and advanced oxidation process. Solvent resistant membrane distillation (SR-MD) was proposed as an energy-efficient alternative to treat these waste streams but its application is hampered by the lack of solvent-resistant membranes, and there is a research gap in studying the feeds with water-solvent mixtures. In this work, ceramic tubular membranes with different pore sizes and structures were molecularly grafted with 1H,1H,2H,2H-perfluorodecyltriethoxysilane to obtain hydrophobic ceramic membranes for SR-MD. The modified membranes exhibited excellent hydrophobicity and solvent resistant properties, and they were tested for SR-MD performance with a wide range of dimethyl sulfoxide (DMSO) feed concentrations, from 3.5 to 85 wt%. The membranes exhibited a high DMSO rejection of >98% and the separation factor of >170, with permeation flux >4.4 kg m−2 h−1 when the DMSO concentration in feed was below 65 wt%. The separation performance was found strongly dependent on the evaporation step and the vapour-liquid equilibrium near the interface. The DMSO rejection was also comparable to pervaporation while the permeation flux was much higher at the feed concentration of 50 wt%. This study establishes the strategy of using SR-MD as a promising membrane process in treating complex industrial wastes with high organic solvent content.