SUMMARY Toxicodendron species are economically and medicinally important trees because of their rich sources of natural products. We present three chromosome‐level genome assemblies of Toxicodendron vernicifluum ‘Dali’, Toxicodendron succedaneum ‘Vietnam’, and T. succedaneum ‘Japan’, which display diverse production capacities of specialized metabolites. Genome synteny and structural variation analyses revealed large genomic differences between the two species ( T. vernicifluum and T. succedaneum ) but fewer differences between the two cultivars within the species. Despite no occurrence of recent whole‐genome duplications, Toxicodendron showed evidence of local duplications. The genomic modules with high expression of genes encoding metabolic flux regulators and chalcone synthase‐like enzymes were identified via multiomics analyses, which may be responsible for the greater urushiol accumulation in T. vernicifluum ‘Dali’ than in other Toxicodendron species. In addition, our analyses revealed the regulatory patterns of lipid metabolism in T. succedaneum ‘Japan’, which differ from those of other Toxicodendron species and may contribute to its high lipid accumulation. Furthermore, we identified the key regulatory elements of lipid metabolism at each developmental stage, which could aid in molecular breeding to improve the production of urushiol and lipids in Toxicodendron species. In summary, this study provides new insights into the genomic underpinnings of the evolution and diversity of specialized metabolic pathways in three Toxicodendron cultivars through multiomics studies.