The genus Fusarium poses significant threats to global food security and safety due to its ability to cause destructive diseases and mycotoxin contamination in staple crops like maize and wheat. Climate change exacerbates these issues by altering environmental conditions—such as increased temperature and humidity—that favor the proliferation and virulence of Fusarium species. Addressing these threats necessitates innovative solutions, including advanced tools that facilitate the identification of targets for effective control strategies. To respond to this challenge, we developed the Fusarium Protein Toolkit (FPT), a web-based resource that enables users to explore the structural and variant landscapes of protein sequences within the Fusarium pan-genome. FPT features both AlphaFold and ESMFold-generated protein structure models from six Fusarium species, accessible through a user-friendly web portal. This toolkit facilitates comparative analysis and functional annotation inference within Fusarium species and lays the foundation for cross-species comparisons between the pathogen (Fusarium) and its cereal hosts (maize and wheat). By providing a common set of tools and models, FPT allows researchers to directly compare protein structures and functions across species, enhancing our understanding of host-pathogen interactions. Utilizing a protein language model, FPT predicts the impact of over 270 million coding variants in two agriculturally significant species, F. graminearum and F. verticillioides. Additionally, it offers variant effect scores for proteins in a Fusarium pan-genome based on 22 diverse Fusarium species, displayed as heatmaps using the PanEffectframework. This comprehensive dataset allows researchers to identify potential targets for breeding disease-resistant crop varieties. Building on this foundation, we used RFdiffusion to predict protein-protein interactions (PPIs) between Fusarium proteins and those of maize and wheat. We’ve identified over 15,700 potential PPIs in maize and 17,700 in bread wheat with this method thus far, and plan to refine our predictions using in silico analyses and experimental validation. By identifying and modeling these interactions, we can gain deeper insights into the mechanisms of pathogenicity and host defense. Future developments will include integrating visualization resources to display PPI networks, further enhancing the toolkit's utility in facilitating cross-species analyses and aiding in the development of innovative control strategies. The Fusarium Protein Toolkit is available at https://fusarium.maizegdb.org.