Rational design of a high-performance defect-free polyamide (PA) layer on a robust ceramic substrate is challenging for forward osmosis (FO) water treatment applications. In this study, we first demonstrated a robust ceramic-based thin-film composite (TFC) FO membrane by engineering a novel nanocomposite interlayer of titanium dioxide and carbon nanotube (TiO2/CNT). The structural morphologies and properties were systematically characterized for different substrates (without interlayer, with TiO2 interlayer, or with TiO2/CNT interlayer) and the corresponding ceramic-based TFC-FO membranes. Introduction of low roughness nanocomposite interlayers with decreased pore size created an interface with improved surface characteristics, favoring the formation of a defect-free nanovoid-containing PA layer with high cross-linking degree. The resulting ceramic-based FO membrane had a water permeability of approximately 2 L/(m2 h bar) and a NaCl rejection of 98%, showing simultaneous enhancements in both compared to the control membrane without an interlayer. Mechanism analysis indicates that such a special nanocomposite interlayer not only provided more active sites for the formation of a thinner defect-free nanovoid-containing PA layer without penetration into substrate but also acted as a highly porous three-dimensional network structure for rapid water transport. This work provides a novel protocol for rational design and fabrication of a high-performance multilayered inorganic FO membrane as well as extended applications in water treatment with enhanced performance.