Complex nature of the interactions between plant, animal, human and ecosystem renders multisectoral transdisciplinary approaches critical to address future food and health risks and challenges. Proteogenomics and organeller proteomics uncover new strategies for one health problems by facilitating discovery of molecular signature of disease and protein biomarkers to multi-host resistance. Fusarium sp., an ascomycetes fungus and multi-host pathogen is a causal agent of vascular wilt in plants, neuronal stress in worm and fusariosis in humans. Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, underlying molecular mechanisms by which this process is regulated against multi-host pathogen remain unknown. We have established the proteo-genomics landscape of a food legume, chickpea and reanalysed the data for worm in healthy and disease state based on DDA library and SWATH-MS with a high-quality spectral library for rapid and deep profiling. Further, with an iTRAQ based workflow combining integrated transcriptomics and metabolomics, we also demonstrated multilayered analyses at the resolution of organellar proteomics and phosphor-proteomic and their application to reveal new insight on the immune signature and pathogenesis during fusariosis. Most excitingly, network analysis identified significant functional modules pointing toward fusarium responsive common mechanism of remodelling, homeostasis and cell death response through divergent regulatory pathways across kingdom.