Secondary metabolites (SMs) are crucial for plant adaptation and human health, yet the regulatory mechanisms underlying their biosynthesis remain incompletely understood. Cornus wilsoniana, a woody oil crop and medicinal plant, is renowned for its rich flavonoid content, yet the genetic and metabolic basis of its secondary metabolism remains largely unexplored. Here, we integrate transcriptomic and metabolomic analyses to dissect the regulatory landscape governing flavonoid biosynthesis during flower bud development. Comparative analyses between high-yield and low-yield genotypes across distinct developmental stages reveal a coordinated reprogramming of flavonoid pathways, with significant shifts in gene expression and metabolite accumulation. WGCNA links critical biosynthetic genes to co-expression modules enriched in hormone signaling, redox homeostasis, and light perception, underscoring the interplay between developmental and environmental cues in shaping metabolic fluxes. Furthermore, comparative genomics reveals 17 candidate genes forming a complete anthocyanin and proanthocyanidin biosynthetic network. Our findings illuminate the molecular framework underlying flavonoid metabolism in C. wilsoniana, providing a foundation for metabolic engineering and genetic improvement strategies aimed at enhancing bioactive compound production for medicinal and agricultural applications.