Organo-montmorillonite (OMMT) was introduced into SEBS-g-MA toughened poly(phenylene oxide)/polyamide-6 (PPO/PA6) blends simply by melt extrusion. The effects of OMMT on morphology, rheology, and mechanical behaviors of toughened PPO/PA6 nanocomposites were studied by scanning electron microscope, transmission electron microscope, capillary rheometer and mechanical tests. The addition of OMMT could decrease the size of dispersed PPO domains in PA6 matrix and melt viscosity of the toughened PPO/PA6 nanocomposites. Besides, exfoliated OMMT also brought significant improvement of tensile properties and heat deflection temperature (HDT), simultaneously. For nanocomposites with exfoliated OMMT, OMMT induced more coreshell toughening particles with the optimized size, and thus, elastomer-OMMT synergistic toughening was achieved in the PPO/PA6 nanocomposites. Consequently, PPO/PA6 nanocomposites with high tensile strength, excellent impact performance, improved HDT, and good processability were obtained.