Recent studies have uncovered critical relationships between host microbiomes, viral infections, and disease. Scripps Research identified dozens of human host proteins essential for SARS-CoV-2 replication, including perlecan, revealing novel antiviral drug targets that may yield pan-coronavirus therapies resistant to viral mutations. In oncology, the microbiome’s role in early tumor development is gaining recognition for its contribution to oncogenesis. Furthermore, metagenomic sequencing detected lung virome shifts preceding hospital-acquired pneumonia onset in critically ill patients, offering potential prognostic biomarkers. These insights hold promise for innovative treatments targeting host-pathogen interactions and microbiome manipulation.