Bioremediation stands at the forefront of sustainable environmental remediation, providing a biologically inspired approach to mitigate pollutants arising from industrial, agricultural, and urban activities. Yet, conventional bioremediation techniques often face constraints related to scalability, fluctuating environmental conditions, and incomplete or inefficient pollutant degradation. This chapter explores the paradigm shift brought about by the integration of advanced molecular tools, particularly genomics and proteomics, which are reshaping the landscape of bioremediation by offering in-depth, systems-level insights into microbial communities, metabolic circuits, and enzymatic dynamics under contamination stress. Commencing with the foundational principles of microbial, phytoremediation, and mycoremediation mechanisms, the chapter comprehensively examines cutting-edge genomic tools, including next-generation sequencing, metagenomics, and functional annotation, to elucidate key genes and community structures involved in pollutant breakdown. Complementary proteomic technologies, such as mass spectrometry and protein interaction mapping, are highlighted for their ability to characterize functional enzymes and stress-related proteins central to remediation processes. The synergy of these omics disciplines, underpinned by bioinformatics and systems biology, lays the groundwork for engineering optimized microbial strains and synthetic consortia with superior degradative potential. Real-world case studies and frontier innovations—from CRISPR-Cas-mediated genome editing to AI-enhanced modeling and nanotechnology-assisted remediation—demonstrate the tangible applications of this integrated approach. Ultimately, this chapter emphasizes the transformative promise of omics-enabled bioremediation in advancing global ecological restoration and sustainability efforts.