The One Health framework, traditionally focused on microbial threats, needs a bold expansion to include the full breadth of microbial diversity-from pathogenic to beneficial-within its ecological and evolutionary context. By shifting focus from disease surveillance to microbial stewardship, an integrative One Health microbiome science approach breaks down traditional silos in microbiome research, accelerating integrative and comparative science to uncover foundational insights into microbial community assembly, stability, and resilience. Ultimately, this will help unlock the full potential of microbiomes to enhance global health and sustainably manage ecosystems.