This work reports new-generation 2D-MoS2 nanosheet-containing polyurethane (PU) composite materials with improved thermo-mechanical stiffness, thermal stability, and fire retardation property. The surface of 2D-MoS2 nanosheets was modified with melamine (M-MoS2), and then PU composites with varying M-MoS2 loadings were synthesized using an in-situ polymerization method. During polymerization, 3-amino-propyl-trimethoxy silane was introduced to create silicate functionality on the PU chains, which further improves the compatibility between PU and M-MoS2. Microscopy studies confirmed the distribution of highly intercalated and agglomerated M-MoS2 nanosheets in the PU matrix. The PU composite containing 5 wt.% M-MoS2 showed a 65% higher storage modulus (at 30C) than that of pure PU. The thermal stability of pure PU was significantly improved (62C) after composites formation. Thermogravimetric analysis in combination with FTIR spectroscopy showed that the PU/M-MoS2 composites release less toxic gases during thermal degradation compared to pure PU. Moreover, the composite containing 5 wt.% M-MoS2 showed improved fire retardation properties, with 45% and 67.5% decrease in the peak heat and total heat release rates, respectively, as compared with those of pure PU. In summary, 2D-MoS2 was shown to have potential as an advanced nano-filler to obtained stiffer PU composite with improved fire retardant property for structural application.