In industries that see rapid and ceaseless changes, the evidence of rich sensing supported by artificial intelligence and advanced manufacturing is quite obvious. In this thrust area, where novel sensors and instrumentation are recognized as the key enabling technology for fuel cycle monitoring, we will look into the success made in other industries and leverage the state-of-the-art technologies to develop the next generation of sensors and instrumentation. Any large-scale problem in today’s complex world demands an innovative solution developed by an interdisciplinary team. We have brought in an integrated collaborative effort of Chemistry, Physics, Electical and Computer Engineering, Materials Sciences, Biostatistics and Medical Informatics, Forest & Wildlife Ecology, and Nuclear and Radiological Engineering.