Various human activities today have an impact on aquatic ecosystems. Wastewater discharged from various sources, including industrial, domestic, agricultural, and mining, contains high concentrations of organic and inorganic pollutants. The wastewater is subjected to various physical, chemical, and biological treatments to mitigate or reduce its impact when it is released into the environment. However, they are not completely effective because there are recalcitrant contaminants that are difficult to remove. More advanced strategies are needed to identify and study the full set of biomolecules produced by microorganisms involved in wastewater bioremediation. Omics approaches are advanced strategies that allow us to study all cellular components of microorganisms (DNA, RNA, proteins, metabolites, etc.) in a global way. The integration of omics approaches in wastewater treatment allows us to understand the interaction of microorganisms with their environment from a global perspective. This leads to the development of new strategies to improve the efficiency of microbial biodegradation of pollutants in wastewater. So, this chapter focuses on developing the most important advanced omics approaches to get a better idea of how microorganisms that can biodegrade wastewater behave to improve the efficiency of removing pollutants. In addition, future perspectives on the integration of omics in the field of wastewater treatment are also discussed.