Wastewater metagenomics is transforming how we monitor microbial communities, offering a powerful and cost-effective approach for pathogen surveillance, antimicrobial resistance (AMR) tracking, and environmental health insights. In Africa, high-throughput sequencing (HTS) of wastewater can serve as an early warning system for infectious disease outbreaks—especially in densely populated areas with limited sanitation—while also supporting discovery of emerging pathogens and novel microbial functions. This overview highlights both the major opportunities and the key challenges, including infrastructure limitations, bioinformatics capacity gaps, variable wastewater composition, and data governance considerations, and outlines the collaborations and investments needed to unlock equitable public health and economic benefits.