Neofusicoccum parvum is a fungal plant pathogen of a wide range of hosts but knowledge about the virulence factors of N. parvum and host–pathogen interactions is rather limited. The molecules involved in the interaction between N. parvum and Eucalyptus are mostly unknown, so we used a multi-omics approach to understand pathogen–host interactions. We present the first comprehensive characterization of the in vitro secretome of N. parvum and a prediction of protein–protein interactions using a dry-lab non-targeted interactomics strategy. We used LC-MS to identify N. parvum protein profiles, resulting in the identification of over 400 proteins, from which 117 had a different abundance in the presence of the Eucalyptus stem. Most of the more abundant proteins under host mimicry are involved in plant cell wall degradation (targeting pectin and hemicellulose) consistent with pathogen growth on a plant host. Other proteins identified are involved in adhesion to host tissues, penetration, pathogenesis, or reactive oxygen species generation, involving ribonuclease/ribotoxin domains, putative ricin B lectins, and necrosis elicitors. The overexpression of chitosan synthesis proteins during interaction with the Eucalyptus stem reinforces the hypothesis of an infection strategy involving pathogen masking to avoid host defenses. Neofusicoccum parvum has the molecular apparatus to colonize the host but also actively feed on its living cells and induce necrosis suggesting that this species has a hemibiotrophic lifestyle.