In recent years, Machine Learning (ML) has become a buzzword in the petroleum industry, with numerous applications which guide engineers in better decision making. The most powerful tool that most production development decisions rely on is reservoir simulation with applications in multiple modeling procedures, such as individual simulation runs, history matching and production forecast and optimization. However, all of these applications lead to considerable computational time and computer resource-associated costs, rendering reservoir simulators as not fast and robust enough, and thus introducing the need for more time-efficient and intelligent tools, such as ML models which are able to adapt and provide fast and competent results that mimic the simulator’s performance within an acceptable error margin. In a recent paper, the developed ML applications in a subsurface reservoir simulation were reviewed, focusing on improving the speed and accuracy of individual reservoir simulation runs and history matching. This paper consists of the second part of that study, offering a detailed review of ML-based Production Forecast Optimization (PFO). This review can assist engineers as a complete source for applied ML techniques in reservoir simulation since, with the generation of large-scale data in everyday activities, ML is becoming a necessity for future and more efficient applications.