The causal agent of mal secco disease is the fungus Plenodomus tracheiphilus, mainly affecting lemon tree survival in the Mediterranean area. Using a fully compatible host-pathogen interaction, the aim of our work was to retrieve the fungus transcriptome by an RNA seq approach during infection of rough lemon (Citrus jambhiri Lush.) to identify crucial transcripts for pathogenesis establishment and progression. A total of 2438 clusters belonging to P. tracheiphilus were retrieved and classified into the GO and KEGG categories. Transcripts were categorized mainly within the “membrane”, “catalytic activity”, and “primary metabolic process” GO terms. Moreover, most of the transcripts are included in the “ribosome”, “carbon metabolism”, and “oxidative phosphorylation” KEGG categories. By focusing our attention on transcripts with FPKM values higher than the median, we were able to identify four main transcript groups functioning in (a) fungus cell wall remodeling and protection, (b) destroying plant defensive secondary metabolites, (c) optimizing fungus development and pathogenesis, and (d) toxin biosynthesis, thus indicating that a multifaceted strategy to subdue the host was executed.