Modern high-throughput molecular and analytical tools offer exciting opportunities to gain a mechanistic understanding of unique traits of weeds. During the past decade, tremendous progress has been made within the weed science discipline using genomic techniques to gain deeper insights into weedy traits such as invasiveness, hybridization, and herbicide resistance. Though the adoption of newer “omics” techniques such as proteomics, metabolomics, and physionomics has been slow, applications of these omics platforms to study plants, especially agriculturally important crops and weeds, have been increasing over the years. In weed science, these platforms are now used more frequently to understand mechanisms of herbicide resistance, weed resistance evolution, and crop–weed interactions. Use of these techniques could help weed scientists to further reduce the knowledge gaps in understanding weedy traits. Although these techniques can provide robust insights about the molecular functioning of plants, employing a single omics platform can rarely elucidate the gene-level regulation and the associated real-time expression of weedy traits due to the complex and overlapping nature of biological interactions. Therefore, it is desirable to integrate the different omics technologies to give a better understanding of molecular functioning of biological systems. This multidimensional integrated approach can therefore offer new avenues for better understanding of questions of interest to weed scientists. This review offers a retrospective and prospective examination of omics platforms employed to investigate weed physiology and novel approaches and new technologies that can provide holistic and knowledge-based weed management strategies for future.