The high-latitude regions of Antarctica remain among the most remote, extreme, and least explored areas on Earth. Still, microbial life has been reported in these environments, with limited information on their genetic properties and functional capabilities. This work combines metagenomic and culture-dependent approaches to investigate the microbial diversity, resistome, virulome, and mobile genetic elements (MGEs) in soils from Union Glacier, a cold desert in West Antarctica. Despite the extreme conditions, several bacterial phyla were found, predominating Actinomycetota and Pseudomonadota, with limited archaeal and fungal taxa. The Union Glacier soil bacterial community is significantly less diverse than those from more accessible Antarctic regions, mainly attributed to scarce moisture. Several resistance and virulence genes were found in Union Glacier soils, and bacterial isolates were characterized that were resistant to up to 24 clinical antibiotics, mainly Pseudomonas, Arthrobacter, Plantibacter, and Flavobacterium. Some isolates produced putative virulence factors, including siderophores, pyocyanins, and exoenzymes with hemolytic, lecithinase, protease, and DNAse activity. This evidence uncovers a largely unexplored resistome and virulome hosted by deep Antarctica’s soil microbial communities and the presence of bacteria with pathogenic potential, highlighting the relevance of One Health approaches for environmental surveillance in this continent.