Feeding the growing human population sustainably amidst climate change is one of the most important challenges in the 21st century. Current practices often lead to the overuse of agronomic inputs, such as synthetic fertilizers and water, resulting in environmental contamination and diminishing returns on crop productivity. The complexity of agricultural systems, involving plant-environment interactions and human management, presents significant scientific and technical challenges for developing sustainable practices. Addressing these challenges necessitates transdisciplinary research, involving intense collaboration among fields such as plant science, engineering, computer science, and social sciences. Here, we present five case studies from two research centers demonstrating successful transdisciplinary approaches toward more sustainable water and fertilizer use. These case studies span multiple scales. Starting from whole-plant signaling, we explore how reporter plants can transform our understanding of plant communication and enable efficient application of water and fertilizers. We then show how new fertilizer technologies could increase the availability of phosphorus in the soil. To accelerate advancements in breeding new cultivars, we discuss robotic technologies for high-throughput plant screening in different environments at a population scale. At the ecosystem scale, we investigate phosphorus recovery from aquatic systems and methods to minimize phosphorus leaching. Finally, as agricultural outputs affect all people, we show how to integrate stakeholder perspectives and needs into the research. With these case studies, we hope to encourage the scientific community to adopt transdisciplinary research and promote cross-training among biologists, engineers, and social scientists to drive discovery and innovation in advancing sustainable agricultural systems.