System informatics analyzes data collected from complex science and engineering systems in different domains, such as manufacturing, energy, logistics, and healthcare. In an attempt to improve and optimize the design, performance, and control of these systems, system informatics research leverages methods from various research areas—including statistics, data mining, machine learning, automation and control, and simulation—and offers great opportunities for interdisciplinary collaboration. With the rapid development of information technologies, the big data collected by ubiquitous sensors has posed new challenges for system informatics research. This installment of Trends & Controversies introduces novel methods and interesting applications of system informatics research in the big data era. We hope the work highlighted here encourages a further dissemination of ideas and collaborative opportunities in this important domain