The synergistic effect of microwave and ultrasound irradiations was evaluated for biodiesel production from microalgae biomass (Nannochloropsis sp.) as raw material. A response surface methodology technique based on central composite design was used to understand the process parametric interdependence and optimize the process reaction variables. Reaction kinetics of algal fatty acid methyl ester (FAME) production was also studied. The optimum reaction conditions were determined as wet algal biomass to methanol ratio of 20 g to 30 mL, 1 wt% catalyst concentration, and 7‐minute reaction time at 140 W of microwave power and 140 W of ultrasound power. The estimated activation energy was 17,298 J/mol⁻¹ K⁻¹ for a first‐order reaction kinetics. This study revealed that microwave energy dissipation at a low rate of 140 W combined with 140 W of ultrasound intensity is adequate to produce FAMEs at a maximum yield of 48.2%. Results from this optimization study suggest that a more detailed and mechanistic energy optimization study is critical to increase the FAME yield and maximize energy benefits.