The present study aims to provide a deep insight into the cavitation intensified biodiesel synthesis under ultrasound irradiation. To reach this aim, alkaline transesterification under low-frequency high-power ultrasound irradiation was studied using an ANFIS (Adaptive Neuro-Fuzzy Inference System), which is a robust technique to identify complex input/output relationships. The changes in the reaction yield (herein output) with the operating conditions (herein inputs) were compared with the behavior of the cavitation bubbles under the same condition. Cavitation behavior was described as a function of hydrodynamic, hot-spot characteristics, oscillation velocity and capacity of cavitation bubbles using mathematical simulation of a lone cavity. Apart from these physical contributions of cavitation bubbles in the biodiesel synthesis system, the work also focused on their chemical contribution by analyzing the diffusion and condensation phenomena during the expansion and compression phases across the bubble interface and the reaction mechanism inside the cavity. The previous results in terms of physical analysis clarified the impact of cavitation on increasing local temperature, generating shock waves, and subsequently increasing the mixing quality in the system under ultrasound irradiation. Meanwhile, the latter results uncovered the equilibrium composition of the chemical compounds inside the cavitation bubbles and demonstrated the behavior of those compounds under supercritical conditions inside the cavitation bubble or the conditions the cavitation bubbles underwent (expansion and compression).