AbstractBackgroundThe Vero cell line is the most used continuous cell line for viral vaccine manufacturing with more than 30 years of accumulated experience in the vaccine industry. Nonetheless, virus production yield with Vero cells remains limited. Therefore, given Vero cell line infection susceptibility to a wide range of viruses, alleviating limitations of viral replication and increasing production kinetics in Vero cells could significantly reduce vaccine production time and cost.Here we review the literature on the development of Vero cells as the most effective manufacturing platform for viral vaccines. Whereas various bioprocess development strategies were proposed to improve the production, this review focuses on the genomic characterization and genetic engineering aspects of Vero cells. Rational design of production cell line emerged as a state‐of‐the‐art approach to significantly enhance Vero cell viral production yield and adaptation to suspension culture which aligns with the global preparedness efforts to accelerate and intensify vaccine production capacity to better respond to pandemic situations and epidemic outbreaks.ConclusionUntil recently, the lack of a reference genome for the Vero cell line has limited the understanding of Vero cells behavior in defined culture conditions as well as host‐virus interactions underlying the affinity of the Vero cell line with emerging and re‐emerging pathogens. Importantly this limited our ability to re‐design high‐yield vaccine production processes using Vero genome editing.