Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. Here, the various ?omics infection systems that include but are not limited to ferrets, mice, pigs and even controlled infection of humans are reviewed. Discussion focuses on recent advances, remaining challenges, and knowledge gaps as it relates to influenza-omics infection outcomes.