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Bud Rot, caused by <i>Phytophthora palmivora</i>, is considered one of the main diseases affecting African oil palm (<i>Elaeis guineensis</i>). In this study, we investigated the in vitro molecular dynamics of the pathogen–host interaction by analyzing gene expression profiles from oil palm genotypes that were either susceptible or resistant to the disease. We observed distinct interactions of <i>P. palmivora</i> with resistant and susceptible oil palms through co-expression network analysis. When interacting with susceptible genotypes, <i>P. palmivora</i> exhibited upregulation of carbohydrate and sulfate transport genes. These genes demonstrated co-expression with apoplastic and cytoplasmic effectors, including cell wall degrading enzymes, elicitins, and RxLR motif effectors. The pathogen manipulated susceptible oil palm materials, exacerbating the response and compromising the phenylpropanoid pathway, ultimately leading to susceptibility. In contrast, resistant materials exhibited control over their response through putative Heat Shock Proteins (HSP) that maintained homeostasis between primary metabolism and biotic defense. Co-expressed genes related to flavonoids, WRKY transcripts, lectin-type receptors, and LRR receptors may play important roles in pathogen control. Overall, the study provides new knowledge of the molecular mechanisms underlying the interaction between <i>E. guineensis</i> and <i>P. palmivora</i>, which can contribute to controlling Bud Rot in oil palms and gives new insights into the interactions of <i>P. palmivora</i> with their hosts.