Invasion ofC. fulvumcauses the most serious diseases affecting the reproduction of tomatoes.Cf-10-gene-carrying line showed remarkable resistance toCladosporium fulvum. To exploit its defense response mechanism, we performed a multiple-omics profiling ofCf-10-gene-carrying line and a susceptible line without carrying any resistance genes at non-inoculation and 3 days post-inoculation (dpi) ofC. fulvum. We detected 54 differentially expressed miRNAs (DE-miRNAs) between the non-inoculation and 3 dpi in theCf-10-gene-carrying line, which potentially regulated plant-pathogen interaction pathways and hormone signaling pathways. We also revealed 3,016 differentially expressed genes (DEGs) between the non-inoculated and 3 dpi in theCf-10-gene-carrying line whose functions enriched in pathways that were potentially regulated by the DE-miRNAs. Integrating DE-miRNAs, gene expression and plant-hormone metabolites indicated a regulation network where the downregulation of miRNAs at 3 dpi activated crucial resistance genes to trigger host hypersensitive cell death, improved hormone levels and upregulated the receptors/critical responsive transcription factors (TFs) of plant hormones, to shape immunity to the pathogen. Notably, our transcriptome, miRNA and hormone metabolites profiling and qPCR analysis suggested that that the downregulation of miR9472 potentially upregulated the expression ofSAR Deficient 1(SARD1), a key regulator for ICS1 (Isochorismate Synthase 1) induction and salicylic acid (SA) synthesis, to improve the level of SA in theCf-10-gene-carrying line. Our results exploited potential regulatory network and new pathways underlying the resistance toC. fulvuminCf-10-gene-carrying line, providing a more comprehensive genetic circuit and valuable gene targets for modulating resistance to the virus.