With an increasing demand for food and renewable energy opposed by climate-driven crop losses, understanding and leveraging plant natural defenses can enable the development of sustainable crop production systems. Plant specialized metabolites are a large and diverse group of molecules that directly contribute to the plants’ fitness and survivability, but are still widely unexplored in many crops. Therefore, we integrate high-throughput omics such as comparative transcriptomic and metabolomic analyses to gain a detailed understanding of the diversity and physiological relevance of specialized metabolites in a range of bioenergy, food, and forage crops. With a focus on terpenoids, we work on the discovery and modification of the underlying biosynthetic networks to develop a new generation of stress-smart varieties advancing sustainable crop production.