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The damaging impact of plant-parasitic nematodes (PPNs) on global agricultural yields prompted Syngenta to launch a nematicide discovery program, resulting in the development of TYMIRIUM® technology. This innovative nematicide and fungicide, featuring cyclobutrifluram as the active ingredient, received its first registrations in 2022. Cyclobutrifluram, a chiral phenyl-cyclobutyl pyridineamide, offers broad-spectrum efficacy against all economically relevant PPNs and soil-borne diseases, particularly Fusarium species. The molecule's discovery journey involved hit identification, lead exploration, and optimization phases, leveraging phenotypic nematicide screening platforms, targeted screening libraries, rapid target identification using biochemical and genetic methods, in vitro assays for structure–activity relationship (SAR) analysis, and homology models for structure-based design. This comprehensive, multidisciplinary approach culminated in the successful discovery of cyclobutrifluram as the key ingredient in TYMIRIUM® technology.