A control system for automatic operation of a hydrocracking unit is shown. The control system includes a control device operable to affect at least one of a yield or a product quality of one or more output oil products provided as outputs of the hydrocracking unit. The control system further includes a controller configured to obtain an objective function that quantifies a value of operating the hydrocracking unit as a function of at least one of the yield or the product quality of the one or more output oil products, use a neural network model to generate a target control device setpoint predicted to optimize the objective function when the hydrocracking unit operates at the target control device setpoint, and operate the control device using the target control device setpoint to modulate at least one of the yield or the product quality of the one or more output oil products.