The increasing complexity and business requirements of operational technology (OT) devices is beginning to break the normal segmentation between information technology (IT) and OT networks. The introduction of industry 4.0 devices such as industrial internet of things (IIoT) and other intelligent industrial devices (IID), virtualized OT systems, OT cloud integration, and artificial intelligence (AI)-driven industrial control systems (ICS) has challenged traditional IT/OT cybersecurity strategies. Industry 4.0 devices are analyzed through the lens of well-regarded models such as the PERA model and confidentiality, integrity, and availability (CIA) security objectives, showing the division between what is needed and traditional cybersecurity countermeasures. In this paper, the practice of CyberInformed Engineering (CIE) is proposed to bridge the gap between IT/OT security, enhance the practice of cybersecurity in this modern age, and reduce the impacts of high consequence events in OT.