In this study, we aimed to analyze the global response to iron in the broad‐range host pathogen Vibrio vulnificus under the hypothesis that iron is one of the main signals triggering survival mechanisms both inside and outside its hosts. To this end, we selected a strain from the main zoonotic clonal‐complex, obtained a mutant in the ferric‐uptake‐regulator (Fur), and analyzed their transcriptomic profiles in both iron‐excess and iron‐poor conditions by using a strain‐specific microarray platform. Among the genes differentially expressed, we identified around 250 as putatively involved in virulence and survival‐related mechanisms. Then, we designed and performed a series of in vivo and in vitro tests to find out if the processes highlighted by the microarray experiments were in fact under iron and/or Fur control. Our results support the hypothesis that iron acts as a niche marker, not always through Fur, for V. vulnificu s controlling its entire life cycle. This ranges from survival in the marine environment, including motility and chemotaxis, to survival in the blood of their hosts, including host‐specific mechanisms of resistance to innate immunity. These mechanisms allow the bacterium to multiply and persist inside and between their hosts.