Novel hybrid nanostructures (HNS) comprising of a mussel-inspired polymer coated metal/metal oxide (M/MO)-carbon nanotubes (CNTs), were successfully synthesized and used to fabricate Thin Film Nanocomposite (TFN) membranes for desalination applications. For comparison, four different M/MO (Aluminium oxide-Al2O3, Iron oxide-Fe2O3, Titanium dioxide-TiO2 and Silver-Ag) nanoparticles (NPs) were in situ synthesized/loaded on the surface of CNTs, and the resultant HNS were further coated with a thin polymeric film of polydopamine (PDA). An intermediate layer of HNS was then deposited on a PES substrate membrane and an interfacial polymerization (IP) process was carried out to render a polyamide (PA) thin layer above the intermediate layer. Both HNS and TFN were characterized using different characterization tools, including fourier transforms infrared spectroscopy (FTIR), zeta potential (ZP), X-ray diffraction (XRD), raman spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), surface hydrophilicity/hydrophobicity, and the performance of nanofiltration (NF) membranes were evaluated against monovalent and divalent salts solutions. The fabricated TFN-NF membranes had higher performance in terms of their permeation characteristics compared to the thin film composite TFC membrane, while maintaining their selectivity against both monovalent and divalent salts solutions with only minor variation depending on the incorporated HNS used to prepare the TFN.