Food production and food security rely heavily on high levels of crop productivity and resilience of crop production under diverse environmental stresses. In order to better understand and apply the knowledge of plant and their associated microbiomes, we have been using a combination of systems biology approaches to integrate metabolomics with other ‘omics strategies. These approaches have led us to develop strategies for improving plant productivity and stress tolerance. This talk will use examples of both metabolomics and genomics-based top-down approaches and hypothesis-driven experimental approaches. I will summarise our findings using integrated approaches to show how plants generate their metabolite diversity for environmental and pathogen stress tolerance and actively reprogram stress hormones. I will next summarize, our discovery of a novel plant hormone-mimicking system used by the fungal pathogen, Magnaporthe of rice blast disease during host invasion in the phyllosphere. I’ll end the talk by sharing our integrative ‘omics work on the tropical fruit, Durian. Overall, these findings provide avenues for developing next-generation options to enhance plant productivity and resilience.