Tomato (Solanum lycopersicum) is a globally significant crop due to its nutritional value and extensive cultivation. However, various pathogens severely impact tomato production, including bacteria, fungi, viruses, and nematodes, resulting in significant yield losses. Developing disease-resistant tomato cultivars is one of the most sustainable methods for successful production. The recent advancements in omics techniques allow for enhanced coverage of plant transcriptomes, proteomes, and metabolomes during pathogen attacks and regulation of the response after infection. Genomics-assisted breeding and gene editing techniques such as quantitative trait loci (QTL) mapping, marker-assisted selection, and CRISPR-Cas9 offer precise methods within the high-throughput method of developing disease-resistant tomato varieties. Transcriptomics provides insights into differentially expressed genes (DEGs) during pathogen attacks. Noncoding RNAs (ncRNAs) regulate gene expression and signaling pathways crucial for plant immunity. On the other hand, proteomics and metabolomics reveal critical proteins and metabolites involved in tomato defense responses. This comprehensive cataloging of omics resources has raised attention to the necessity of integrating omics methods to ensure effective resource use and an enhanced understanding of the molecular process. The information provided in this chapter will help us understand tomato defense responses against diseases, the molecular mechanisms involved in plant disease resistance, and the effective utilization of omics resources for tomato crop improvement.