Wheat cultivation in Northeast India remains underdeveloped despite increasing demand for cereal diversification and climate-resilient cropping systems. This study evaluates the agronomic optimization, regional adaptability, stress mitigation, nutritional potential, industrial suitability, and policy relevance of two major wheat varieties—Sonalika and HD 2967—across Meghalaya, Nagaland, Arunachal Pradesh, and Tripura. Multi-location field trials under randomized block design were conducted for two rabi seasons. Results revealed that optimized sowing (15–30 November), integrated nutrient management (120:60:40 NPK kg ha⁻¹), and targeted drainage practices increased yield by 19–28% compared to traditional practices. HD 2967 exhibited superior yield potential (3.85 t ha⁻¹), while Sonalika showed early maturity and stress adaptability. Grain protein ranged from 11.5–13.8%, with significant suitability for bread and biscuit industries. The integrated framework demonstrates strong potential to enhance regional wheat productivity and strengthen food security under climate variability.