This study reports the landscape of virulence factors, antibiotic resistome, and mobilome in the sediment and seawater microbiota residing hadal environment of the deepest ocean bottom on earth. Our work unravels the contrasting and unique features of virulence genes, ARGs, and MGEs in the Mariana Trench bottom, providing new insights into the eco-environmental and biological processes underlying microbial pathogenicity, resistance, and adaptative evolution in the hadal environment.