This study investigates the fabrication and optimization of a novel thermoplastic vulcanizate (TPV) nanocomposite consisting of organo-modified layered double hydroxide (O-LDH) and a polypropylene (PP)/polybutadiene rubber (PBR) base for the first time. O-LDH was prepared by condensation reaction between an aminosilane-modified LDH (Si-LDH) and both maleic-anhydride-grafted-liquid polybutadiene (LPBR-g-MA) and maleic-anhydride-grafted polypropylene (PP-g-MA). A two-comp onent mixture consisting of LPBR-g-MA and PP-g-MA (weight ratio:60/40) (Comp-g-MA) was used as the compatibilizer agent, and bis-(triethoxysilylpropyl)-tetrasulfid (TESPT) was employed as the vulcanizing agent which was activated in the presence of MA. Response surface methodology (RSM) integrated by central composite design (CCD) was utilized to maximize the gel content and minimize the number-averaged rubber particle size (NARPS) of TPV-Nanocomp osite by optimizing the amounts of Comp -g-MA, TESPT and O-LDH. The outcomes revealed that increasing the O-LDH and Comp -g-MA up to a certain amount, decreased the size of the vulcanizate PBR domains due to the formation of a strong interface, but it caused an increasing trend for the %gel up to a maximu m value. The optimized TPV sample (OTPV) was obtained using 8.2 % Comp -g-MA, 5.8 % O-LDH and 2.5 % TESPT and exhibited 50.4 % of gel content and 135.6 μm of NARPS. OTPV showed superior properties in terms of morphological stabilization, thermal stability and oil-resistance due to the synergistic effect of Comp -g-MA and O-LDH components into the PP/PBR blends.