The multi-omics landscape revolutionized the post-genomics era through present-day advancements in high-throughput technologies. The “-omics,” constituting genomics, ionomics, transcriptomics, proteomics, metabolomics, and microbiomics, delineates the comprehensive studies of biological systems. In agriculture, genomics delineates the complete study of entire DNA content in plants. The structural and functional genomics prioritize the implementation of molecular markers, mapping and sequencing approaches among agricultural crops to tackle with biotic and abiotic stresses. The functional genomics generally deals with transcriptomics involving the study at RNA level comprising of coding (mRNAs) and noncoding messenger RNAs (ncRNAs), and splice variants. Proteomics employs the use of high-throughput methods, viz. mass spectrometry and protein–protein interaction studies to elucidate the protein expression levels to reveal the functional proteome. Ionomics deals with the analysis of essential and non-essential mineral ions within biological systems that are crucial in plants for growth and survival. The analytical methods in metabolomics reveal the comprehensive study of primary and secondary metabolites in plant extracts. Microbiomics explores microorganisms inhabiting diverse environments to compute the beneficial microbiota among agricultural crops through high-throughput methods and bioinformatics approaches. Collectively, the coupling of all the omics methods unveils the complexities of biological systems at molecular level in agricultural crops. Here, we discuss the role multi-omics play in conferring crop improvement for sustainable agriculture.