Avian influenza A viruses pose ongoing threats to human and animal health, with H7 subtypes causing outbreaks globally. In Mexico, highly pathogenic H7N3 viruses have circulated in poultry since 2012, causing sporadic human infections. Here we analyzed genetic markers in hemagglutinin sequences from Mexican H7N3 isolates and conducted serological assays on human populations with poultry exposure. Our results show conserved avian-like receptor binding sites, thus limiting human adaptation, alongside antigenic drift and acquisition of glycosylation sites likely driven by vaccination. Serological testing of 1103 individuals revealed no detectable antibodies against H7N3, indicating a na?ve population. Phylogenetic analyses revealed multiple virus clades circulating regionally. These findings suggest that while current H7N3 viruses have limited capacity for sustained human transmission, the lack of population immunity underscores the importance of continued surveillance and risk assessment to mitigate potential pandemic threats.