Abstract：Biological wastewater treatment has developed for more than 100 years, and new concepts about future wastewater treatment have been put forward worldwide. Environmental biotechnology is still the key contributor for wastewater management. However, these biotechnologies are facing challenges due to stringent discharging standards and the removal of emerging pollutants. Here, a new concept of microbial niche nexus sustaining biological wastewater treatment was proposed, which can achieve the efficient removal of known and unknown pollutants through tuning microbial niches to accommodate diverse microbial communities. Microbial niche nexus could be applied to solve emerging challenges besides infrastructure construction. In addition, the co-enrichment of r/K-strategists and the establishment of microenvironments with substrate gradients could be adopted for the design and operation of biological wastewater treatment processes. Finally, future development and perspectives were presented through aspects of microbial enrichment, microbial function and metabolism identification, system design and operation control, and new technology development and application.