This study reports the continuous production of H2 from the wastewater effluent of the biodiesel industry in a medium containing water under supercritical conditions. The effects of temperature and feed flow rate on the generation of hydrogen were evaluated and optimized. At a temperature of 700 °C and a 17.5 mL/min feed flow, a total gas flow of 5541 NmL/min was achieved. Among all identified gases, hydrogen represented the highest molar fraction of 73%. Under optimized conditions, a H2 yield of 357 NmL/geffluent feed was observed. The experimental results indicate a significant increase in the H2 production at the highest experimented temperatures. On the other hand, the feed flow only slightly influenced the process within the assessed range but showed a tendency to increase the H2 production at the highest values. Finally, information on energy efficiency optimization and scale-up are presented, and at the same time, different designs for industrial implementation of the hydrothermal gasification process are proposed.