A regional susceptibility study in North East India revealed significant variation in insecticide tolerance among Hyposidra talaca (H. talaca) and Eterusia aedea (E. aedea ) populations. The Dooars region showed the highest tolerance for both the pests while Cachar (forH. talaca) and the organic tea estate of terai region (for E. aedea) exhibited the lowest. An insecticide resistance map has been generated for H.talaca. Detoxifying enzyme analysis for cytochrome P450, general esterase, glutathione S-transferase revealed a strong positive correlation with insecticide tolerance, indicating metabolic detoxification contributes to resistance. A synergistic bioassay with PBO and Deltamethrin showed increased mortality, suggesting the role of cytochrome P450 in resistance. Total body lipid analysis of H. talaca larvae showed a significant rise in fatty acids from the 1st to 3rd instars, stabilizing thereafter. This suggests developmental modulation of energy allocation and membrane composition, potentially aiding defense. SEM studies showed progressive skin thickening with larval development in both tea looper and red slug, correlating with reduced insecticide penetration and effectiveness. Transcriptomic analysis of resistant H. talaca revealed a multi-tiered detoxification system with strong upregulation of CYP450s (14.17-fold), esterases (13.41-fold), and GSTs (8.37-fold), supported by corresponding enzymatic activity increases. Additional genes like UGTs, ABCC4 transporters, heat shock proteins, and cuticular proteins were also upregulated, indicating roles in xenobiotic handling, stress response, and reduced pesticide penetration. Metabolomic analysis supported transcriptomic findings, showing elevated carboxylic acids, glycosylated compounds, and primary alcohols in resistant populations. Activated pathways included glutathione and porphyrin metabolism, and fatty acid degradation, highlighting metabolic reprogramming in detoxification.