<p>The growing demand for freshwater, coupled with the increasing volume of industrial and municipal wastewater, has intensified the need for sustainable and eco-friendly reclamation strategies. Recent advancements in microbial biotechnology have emerged as promising tools for developing cost-effective, efficient, and environmentally sustainable wastewater treatment (WWT) strategies for reuse and safe disposal. This mini-review explores current innovations, such as microbial consortia, bioaugmentation, and the microalgae-bacteria nexus, which have shown promising results in nutrient removal, enhanced degradation of complex pollutants (including emerging contaminants), and biomass valorization. Moreover, bioelectrochemical systems, such as microbial fuel cells (MFC) and microbial electrolysis cells (MEC), have revolutionized WWT by facilitating pollutant degradation while simultaneously generating bioelectricity or biohydrogen. This article also critically examines the role of CRISPR-based tools and ‘omics’ approaches, which have enabled the development of novel microbial strains and degradative pathways, enhancing wastewater reclamation in challenging environments. Furthermore, advancements through the integration of multi-omics and artificial intelligence, digital twins, and Internet of Things (IoT) for microbial optimization and real-time process control are discussed. The review highlights the role of microbial systems in resource recovery, supporting a circular economy by transforming wastewater into valuable bioresources. Additionally, this review addresses the major challenges and proposes future research directions for effective wastewater treatment. The novelty of this manuscript is that no single review explores the cutting-edge microbial biotechnologies for wastewater reclamation, uniquely integrating CRISPR-Cas genome editing, multi-omics analyses, and artificial intelligence-driven optimization to advance pollutant degradation and real-time process control in one place. This study concludes that by implementing multi-omics and artificial intelligence (AI)-driven optimization process for wastewater treatment can be effective towards wastewater treatment while simultaneously minimizing the environmental pollution.</p>