Powdery mildew is a serious problem in tomato production; therefore, the PM-resistant tomato inbred line, ‘63187’, and the susceptible tomato variety, ‘Moneymaker (MM)’, were used as experimental materials for the combined analysis of transcriptome and widely targeted metabolome on tomato leaves at 0 h post inoculation (hpi), 12 hpi, and 48 hpi. The results indicated that 276 genes were expressed in all treatments, and the K-means cluster analysis showed that these genes were divided into eight classes in ‘63187’ and ten classes in ‘MM’. KEGG enrichment showed that amino acid metabolism, signal transduction, energy metabolism, and other secondary metabolites biosynthesis pathways were significantly enriched. Interestingly, the analysis of WRKY family transcription factors (TFs) showed that the expression of four TFs in ‘63187’ increased with no obvious change in ‘MM’; and the expression of one TF in ‘MM’ increased with no obvious change in ‘63187’. The combined analysis revealed that both phenylpropanoid biosynthesis and flavonoid biosynthesis pathways were enriched in ‘63187’ and ‘MM’. In ‘63187’, six metabolites involved in this pathway were downregulated, and four genes were highly expressed, while in ‘MM’, three metabolites were upregulated, four metabolites were downregulated, and ten genes were highly expressed. These metabolites and genes might be candidates for PM resistance or susceptibility in subsequent studies. These results provide favorable molecular information for the study of the different resistances of tomatoes to PM, and they provide a basis for the breeding of tomato varieties resistant to PM.