Nowadays, biodiesel is promoted as an alternative and renewable fuel. The mass-transfer limited transesterification reaction is commonly used for biodiesel production, but it could benefit from process intensification technologies. The Simultaneous Mixer-Separator (SMS) is a novel process intensification reactor capable of integrating the mixing and separation of reactants within a single unit. The current study aims to determine the ideal parameters for continuous biodiesel production using an SMS setup that was exclusively designed and fabricated in-home for enhanced biodiesel production. The research statistically analyzed the effect of the space between the rotor and the bottom of reactor ( h ) (0.7, 1.0, 1.3 cm), the diameter ratio between the rotor and the stator ( Dr/Ds ) (0.5, 0.7, 0.9), and the frequency of the rotor’s rotary speed ( R f ) (20, 40, 60 Hz) on biodiesel yield using the Response Surface Methodology (RSM). Optimal oil to fatty acid methyl ester(FAME) conversion of 93.2% and the optimal volumetric production rate of 1,980 (kg FAME/m 3 ·h) were obtained by setting the SMS to a rotational frequency of 39 Hz, an h of 0.7 cm, and a D r /D s of 0.85.