ABSTRACT Fusarium proliferatum is a widespread phytopathogenic fungus capable of infecting a broad spectrum of crop species. This study aimed to elucidate the basis of host adaptation and pathogenicity in F . proliferatum through a comprehensive pan‐secretome analysis of nine isolates collected from diverse host plants. Transcriptomic and proteomic data were further incorporated to assess in planta expression and validate the biological relevance of secreted proteins. The analysis revealed 9241 predicted secreted proteins, clustered into 1448 groups. Among these, 1319 clusters were conserved across all isolates and constituted the core secretome, while 129 were variably present and 31 were unique to individual isolates. Functional characterisation indicated a conserved enrichment of carbohydrate‐active enzymes (CAZymes), peptidases and effectors, many of which were transcriptionally upregulated during host infection. Several isolate‐specific proteins, including unique effectors and enzymes, exhibited high sequence similarity to homologues in other Fusarium species, suggesting acquisition via horizontal gene transfer (HGT). These findings indicate that F . proliferatum employs a dual virulence strategy comprising a conserved core secretome for general pathogenicity and lineage‐specific secretory proteins for host‐specific interactions. This dynamic secretome architecture underpins the pathogen's adaptability and virulence across a wide host range and offers promising targets for crop‐specific disease management strategies.