A comprehensive integrative multiomics analysis of astronaut biospecimens from Inspiration4, Polaris Dawn, and Ax-2 missions has unveiled consistent molecular signatures associated with spaceflight. Researchers applied advanced proteomics, epigenomics, transcriptomics, and metabolomics, elucidating alterations in stress-response pathways, immune signaling, mitochondrial function, and DNA repair mechanisms. CRISPR screens identified potential therapeutic targets for mitigating health risks during prolonged space travel. Presented at the ASHG 2025 conference, these findings provide critical temporal and mechanistic insights to enhance astronaut health monitoring and develop countermeasures for future deep-space exploration missions.