Plant secondary metabolites act as key ecological filters that constrain the chemical niche of herbivorous arthropods, underpinning striking interspecific variation in host range breadth. For instance, the extremely polyphagous Tetranychus urticae feeds on more than 1,200 host plants, whereas the specialist Panonychus citri is restricted to about 120 hosts. Because polyphagous species often show higher speciation potential and increased risks of pesticide resistance, they pose major threats to agricultural production. Understanding how polyphagous spider mites adapt to diverse plant secondary metabolites and achieve broad host ranges therefore represents an important question in agricultural ecology. Ecological analyses of host shifts in T. urticae revealed significantly adaptive differences across host plants. Integrative transcriptomic and proteomic analyses were conducted to identify key functional genes involved in rapid adaptation during host shifting, while metabolomic profiling was used to characterize the substantial metabolic reprogramming. Candidate proteins from T. urticae were heterologously expressed in a Sf9 expression system, and their metabolic activities toward representative plant secondary metabolites including alcohols, phenols, terpenoids, furanocoumarins, alkaloids, and flavonoids were characterized using LC-MS/MS. These metabolic functions were compared with those of homologous P450 genes from the P. citri. Finally, key functional genes were validated through gene knockout and transgenic assays, thereby systematically elucidating the ecological mechanisms underlying host-range expansion in spider mites T. urticae showed strong host-dependent variation in adaptability, and its broad host range was largely driven by marked upregulation of the CYP392 family to detoxify diverse plant secondary metabolites. Within this family, functional divergence was evident: 392B efficiently metabolizes alkaloids, 392E primarily targets coumarins, and 392C/D exhibits broad metabolic capacity across multiple compound classes. By contrast, P. citri relied predominantly on the 392A subfamily to metabolize alcohols, furanocoumarins, and terpenoids, but showed limited capacity toward alkaloids and flavonoids. Notably, the extreme expansion of CYP392 in T. urticae, especially 392B/D, enhances alkaloid detoxification, thereby facilitating its extreme polyphagy and ongoing host- range expansion.