Viral diseases significantly impact the productivity and quality of vegetable crops, posing a major challenge to global food and nutritional security. Traditional control methods, such as chemical treatments, vector management, and crop rotation, offer limited success due to the rapid evolution of viruses and their wide host range. Biotechnological interventions have emerged as effective and sustainable strategies for developing virus-resistant vegetable crops. Genetic engineering, RNA interference (RNAi), CRISPR/Cas genome editing tool, and marker-assisted selection, which enable precise manipulation of host or viral genes to confer resistance, have been discussed in this book chapter. Transgenic approaches involve the introduction of viral coat protein genes, movement protein genes, or other viral sequences into plants to trigger pathogen-derived resistance (PDR). RNAi-based strategies use small interfering RNAs (siRNAs) or hairpin RNAs to silence essential viral genes, effectively reducing viral replication. Recent advancements in CRISPR/Cas systems have opened new avenues for editing plant susceptibility genes or viral genomes, providing a targeted, nontransgenic method for inducing resistance. Several successful applications of biotechnological interventions have been demonstrated in vegetable crops such as tomato, pepper, cucumber, and squash against viruses such as tomato yellow leaf curl virus (TYLCV), cucumber mosaic virus (CMV), and zucchini yellow mosaic virus (ZYMV). Biotechnological intervention allows for the pyramiding of resistance traits, enhancing durability and broad-spectrum protection. Biotechnological tools offer promising, eco-friendly alternatives to traditional methods, paving the way for the development of virus-resistant vegetable varieties and sustainable agricultural practices.