Due to the increasing global food demand under climate change scenario, there is an urgent need for the development of climate-resilient, high-yielding, disease-resistant crop varieties that can perform well under diverse agroecological conditions. Genotype × environment (G × E) interactions significantly influence crop performance, making it essential to integrate G × E analysis into plant breeding programs. In this chapter, we explore the importance of incorporating G × E analysis, mainly in the context of biotic stresses, into multi-environment trials (METs) for crops like wheat, rice, and maize. Several case studies demonstrate how neglecting biotic stress in G × E assessments can lead to inaccurate conclusions about genotype adaptability and stability. We discuss strategies to integrate disease and pest pressures into trial designs, balance yield potential with resistance, and apply statistical tools like genotype and genotype × environment (GGE) biplot and additive main effects and multiplicative interaction (AMMI) models for precise selection. This chapter also highlights how advances in marker-assisted and genomic selection, combined with participatory breeding and pathogen monitoring, can be leveraged to enhance durability of resistance. By adopting evolution-informed breeding strategies and expanding METs to include hotspot environments, crop breeders can more effectively address the challenges posed by dynamic biotic stress factors, ultimately facilitating the development of climate-resilient, farmers preferred cultivars and promoting sustainable crop production under diverse and evolving agroecological conditions.