Critical infrastructure, including advanced manufacturing (Industry 4.0), energy networks, healthcare, and water management systems, has been increasingly connected to the Internet, especially since the recent pandemic. Critical infrastructure, when connected to the networks, allows remote control, data processing on the cloud, and collaboration with other systems. However, the critical infrastructure's network connectivity raises serious challenges. Recent cyberattacks on critical infrastructure, including US water systems and energy pipelines, demonstrated the risk of such network-connected critical infrastructure. Network latencies involved in the time-sensitive systems in critical infrastructure render the timely handling of critical tasks problematic. Moreover, it worsens when combined with IoT and embedded systems challenges, including resource constraints, heterogeneity, scalability, and operation in an open environment. This talk will introduce my multi-disciplinary research approaches to building safe, effective, and connected critical infrastructure deployed at scale. I will present an open-source platform for providing essential security processes for connected critical infrastructure and the IoT, along with its network architectures resilient against availability threats such as distributed denial of service (DDoS) attacks. I will discuss my full-stack methodology for real-time and efficient critical infrastructure, from computer architecture to programming models. I will also introduce my ongoing and future research work for dealing with challenges in network communication of distributed critical infrastructure.