Vegetable-infecting viruses represent a persistent, notorious, and fast-evolving threat to global crop production, driven by their high genetic variability and rapid adaptation to host defences. The molecular evolution of these viruses, mainly by mutation, recombination, and host–vector co-adaptation, has caused an emergence of variants that can break resistance, undermining the durability of resistance incorporated into widely cultivated vegetables such as tomato, pepper, and cucurbits. This chapter synthesizes current insights into the evolutionary dynamics of key viral families, including Potyviridae, Geminiviridae, Tospoviridae, and Tobamoviridae, with a focus on mechanisms that underlie viral diversification and resistance evasion. Additionally, we examine plant-defence mechanisms ranging from classical R gene-mediated recognition, RNA silencing pathways, and novel genome-editing approaches. By integrating evolutionary insights with advances in breeding and biotechnology, we emphasize options for creating persistent virus resistance, such as gene pyramiding, targeting conserved viral components, and predictive resistance deployment guided by virus monitoring and population genomics. Understanding the interplay between viral evolution and plant immunity is essential for designing robust plant-defence strategies to encounter emerging viral challenges and agroecosystem pressures.