The extensive usage of rigid polyurethane foam (RPUF) as an energy-saving building materials in construction has raised concerns about fire risks and toxic hazards. To address these challenges, a melamine-derived polyol (MADP) was synthesized using the Mannich reaction, resulting in inherently flame-retardant RPUF materials with the introduction of flame-retardant functional groups. Furthermore, a novel MoS2-Cu2O nanohybrid was prepared and employed to enhance flame retardancy and suppress smoke toxicity in RPUF through a cooperative effect with expandable graphite (EG). The resulting M-RPUF/EG/MoS2-Cu2O nanocomposite exhibited remarkable fire safety, as evidenced by significant reductions in peak heat release rate (PHRR), total heat release (THR), total smoke production (TSP), and peak carbon monoxide (CO) release, amounting to 76.9 %, 64 %, 82 %, and 99 % respectively, compared to pristine RPUF. Furthermore, the nanocomposite effectively addressed interfacial defects and significantly enhanced the mechanical property and thermal stability. The significant improvement in fire safety is mainly ascribed to the catalytic charring effect of MADP and EG, as well as the catalytic oxidation of MoS2-Cu2O nanohybrids, resulting in the formation of a thermally stable protective layer in the condensed phase. Based on these results, the integration of the tri-phase flame retardant system holds great potential for advancing the development of fire-safe polyurethane materials.