A long-standing quest in materials science has been the development of tough epoxy resin nanocomposites for use in numerous applications. Inspired by nacre, here we report tough and conductive MXene/epoxy layered bulk nanocomposites. The orientation of MXene lamellar scaffolds is enhanced by annealing treatment. The improved interfacial interactions between MXene lamellar scaffold and epoxy through surface chemical modification resulted in a synergistic effect. Tailoring the interlayer spacing of MXene nanosheets to a critical distance resulted in a fracture toughness about eight times higher than that of pure epoxy, surpassing other epoxy nanocomposites. Our nacre-inspired MXene/epoxy layered bulk nanocomposites also show high electrical conductivity that provides self-monitoring capability for structural integrity and exhibits an excellent electromagnetic interference shielding efficiency. Our proposed strategy provides an avenue for fabricating high-performance epoxy nanocomposites.