Almost all higher plants are susceptible to flooding stress. Slow gas exchange and low light conditions after submergence are the major factors that have detrimental effects on plant growth and development, limiting crop productivity worldwide. Furthermore, an increasing population and global climate change have necessitated the development of flood-resistant crops. Recent advances in systems biology approaches like transcriptomics, proteomics, metabolomics, transgenomics, and phenomics have enabled us to study various stress responses of crops at the molecular level. Integrating these high throughput approaches with the QTL/genes associated with flooding stress has accelerated the identification of novel and robust markers for the trait. This chapter attempts to provide a detailed discussion on the use and challenges in the practical implementation of these ‘omics-based’ techniques for the characterization of flooding-responsive mechanisms in various agronomically important crops.