"Potato (Solanum tuberosum) is one of the major non-cereal staple food crops grown across the world. Canada produces 4.4 million tonnes of potato. The major constraints in potato production are the biotic and abiotic stresses. Among the biotic stresses, late blight of potato is one of the destructive diseases, caused by an oomycete, Phytophthora infestans. Late blight of potato causes up to 40% yield loss worldwide. Resistance to late blight is either qualitative or quantitative. Even though quantitative resistance is durable, the genetic bed rock underlying resistance is not well deciphered, which limits its applications. The objective of this study was to identify the resistance genes and their mechanisms, in a resistant genotype (Libertas) and a commercial susceptible genotype (AG704). The first study aimed at transcriptomics and metabolomics to identify the induced resistance related metabolites and genes, including the large impact transcription factors which regulate these genes and metabolites that are in higher fold change in a resistant genotype than in a susceptible genotype. A total of 160 induced metabolites and 611 induced genes were identified. A Transcription Factor (TF) enrichment study identified a total of 134 regulatory TFs, which were highly enriched in the promoters of induced genes. A correlation study among the induced genes further mapped several primary and secondary TFs. Among these bHLH66, MYB61, NAC56, WRKY51, MYB like, ERF RAP2-3 and MADS-box AGL15 had regulating sites in more than 208 downstream genes, of which many were secondary TFs. Hence, a two-tier transcriptional regulation of defense response genes was mapped. The metabolic profiling identified Hydroxycinnamic acid amides (HCAAs). Feruloylagmatine was highly accumulated in the resistant genotype post pathogen inoculation. Two major genes StACT1 and StACT2 which might be responsible were characterized by gene sequencing, qPCR and in silico protein docking data and it revealed the StACT2 gene to be mainly responsible for feruloylagmatine accumulation in potato. We found a NAC TF regulating StACT2 promoter region and it was identified as NAC72, which was accumulated more in the resistant than in the susceptible genotype. When the NAC72 CDS and promoter regions were sequenced a mutation was found in the promoter of NAC72. This gene was edited in a late blight susceptible commercial genotype, AG704, to enhance resistance. The expressions of genes StACT2 and NAC72 were significantly increased, however, the disease severity showed no significant difference. It is possible that there may be a missing chain in the hierarchy of genes involved in the regulation and/or in the metabolic pathway network to synthesize the metabolite feruloylagmatine, which is known to enhance disease resistance through deposition of these metabolites to reinforce the secondary cell walls, thus containing the pathogen to initial infection area. Discovery and editing of other mutated gene(s) should enhance feruloylagmatine production, as in resistant genotype. The other genes identified here also can be used in future for genome editing to increase RR metabolite accumulation in potato to enhance late blight and other disease resistance in potato"--