This work explores the feasibility of titanium dioxide (TiO2) for its application in thumba oil transesterification, where a reactor was integrated with hydrodynamic cavitation (HC). TiO2 nanoparticles were synthesised using the ultrasound-assisted sol-gel method by varying the operating conditions. The synthesised TiO2 was found to be in the pure anatase phase. The smallest particle diameter was found to be 8.42 nm under optimised conditions. The consequences of various operating variables (inlet pressure and HC system geometry) on the triglyceride conversion were studied in the HC system. The Gas chromatography (GC-FID) analysis of biodiesel confirmed its synthesis. Orifice plate B with three 2-mm holes resulted in the highest cavitational yield of 9.1 × 10−6 mol.L/J at 5 bar. Under optimised process parameters, a maximum conversion of 71.8% was achieved at 5 bar within 1 h in an HC system. The experimental data reasonably fit 1st order reaction kinetics concerning alcohol and 2nd order kinetics concerning thumba oil. The energetic analysis shows that the highest energy consumption was 16 kWh/m3, much less than the conventional method at 500 kWh/m3. Thumba methyl ester prepared using this novel accelerated technique exhibited time savings and energy coherency, building the operation more resource-efficient.