For decades, studies have been conducted to understand and improve how humans and machines interact; yet, the process systems engineering field often focuses on algorithms that do not explicitly account for human actions in the decision-making process. The article presents a broad view of Human-in-The-Loop (HiTL) technology: how HiTL is viewed by different disciplines, the role of cognitive science in understanding fundamental aspects of human factors and human-machine interaction, which are questions that remain open-ended, and how manufacturing should include a more technologically updated and ethical use of human factors to realize the true potential of Industry 4.0. A Smart Control Room framework is presented with preliminary results and future directions to explicitly consider the HiTL in process operations.