This study investigates the molecular pathogenesis of Ceratocystis manginecans, a fungal pathogen responsible for wilt and canker disease in Acacia mangium. Using a TMT-based quantitative proteomics approach, protein expression was profiled at early stages (1 h and 24 h post-inoculation) following infection with two fungal isolates, CAM and CEP. A total of 205 proteins were identified, with 105 differentially expressed across conditions. The results highlight key virulence-related processes such as DNA repair, oxidative stress response, and host-specific metabolic adaptation. This dataset reveals valuable protein-protein interaction networks that underpin pathogenicity and may inform strategies for disease control in forest plantations.