Vanilla planifolia, the main species cultivated for vanilla production, is severely threatened by Fusarium oxysporum f. sp. radicis-vanillae (Forv), the causal agent of root and stem rot. Given the limited efficacy of current control methods, the development of resistant cultivars requires a better understanding of the molecular mechanisms underlying host defence. In this study, we investigated the very early transcriptional responses of V. planifolia to Forv infection by comparing the resistance genotype CR0020 to the susceptible CR0040. A factorial RNA-seq design was implemented on root tissues sampled at 4, 8 and 12¿h post-inoculation (hpi), and combined differential expression analysis, expression clustering and gene co-expression network inference. The resistant genotype CR0020 displayed a rapid and extensive transcriptional reprogramming between 4 and 8 hpi, marked by early activation of signalling pathways, redox regulation, phenylpropanoid metabolism and coordinated induction of multiple transcriptional regulators. In contrast, CR0040 exhibited a markedly attenuated response during this early phase. At 12 hpi, CR0020 mounted a strong genotype-specific response, with 577 genes induced upon inoculation compared with only 93 in CR0040, reflecting a structured and multilayered defence programme. Network analysis identified key regulatory hubs and revealed constitutive transcriptional differences between genotypes, including a small set of genes overexpressed in CR0020, consistent with a preconditioned transcriptional state. Overall, these results demonstrate that resistance to Forv in V. planifolia relies on a pre-activated, early, coordinated and multilayered transcriptional response continuum linking pathogen perception, regulatory network activation and defence execution and identify candidate genes and modules relevant for resistance breeding.