Salmonella Agona (S. Agona) is a foodborne pathogen that caused recurrent multistate outbreaks associated with cereal in 1998 and 2008, underscoring the endurance of Salmonella in low-moisture food (LMF). The whole genome sequencing revealed that it persisted in the LMF industry for a decade, then resurfaced as a virulent strain and caused outbreak. In this study, we aimed to determine the molecular mechanism of survival of S. Agona in LMF and its impact on phenotypes. RNA-seq was used to compare the adaptability of this pathogen in an extreme environment. There were 1114 differentially expressed genes (DEGs) in S. Agona in response to desiccation stress (Padj < 0.01, |log2FoldChange| >1), with 646 downregulated and 468 upregulated. Functional analysis of downregulated DEGs revealed that most of the genes were associated with metabolic pathways, followed by translation, suggesting slower growth in the surviving population. We observed that virulence genes, including those associated with the Salmonella Pathogenicity Island, were not expressed initially, but showed upregulation after 24 h. Among the upregulated operons/genes, kdp/ccm/tisB were directly associated with growth and metabolism. kdp has the regulatory function to reduce replication, ccm is associated with reducing the consumption of molecular oxygen, and tisB with persister formation. We knocked out three operons/gene and assessed the surviving capability of mutants under desiccation stress. An approximate 1-2 log reduction (P > 0.05) was noticed in the mutant's survival compared with wild type. This transcriptome data suggests that S. Agona survives in low-moisture food by conserving energy, lowering metabolism, and reducing replication.