Extreme environments are excellent places to find microorganisms capable of tolerating extreme temperature, pH, salinity pressure, and elevated concentration of heavy metals and other toxic compounds. In the last decades, extremophilic microorganisms have been extensively studied since they can be applied in several fields of biotechnology along with their enzymes. In this context, the characterization of heavy metal resistance determinants in thermophilic microorganisms is the starting point for the development of new biosystems and bioprocesses for environmental monitoring and remediation. This work focuses on the isolation and the genomic exploration of a new arsenic-tolerant microorganism, classified as FL18. The bacterium was isolated from a hot mud pool of the solfataric terrains in Pisciarelli, a well-known hydrothermally active zone of the Campi Flegrei volcano near Naples in Italy. FL18 showed a good tolerance to arsenite (MIC value of 41 mM), as well as to other metals such as nickel (MIC 30 mM), cobalt, and mercury (MIC 3 mM and 17 μM, respectively). Signatures of arsenic resistance genes (one arsenate reductase, one arsenite methyltransferase, and several arsenite exporters) were found interspersed in the genome as well as several multidrug resistance efflux transporters that could be involved in the export of drugs and heavy metal ions. Moreover, the strain showed a high resistance to bacitracin and ciprofloxacin, suggesting that the extreme environment has positively selected multiple resistances to different toxic compounds. This work provides, for the first time, insights into the heavy metal tolerance and antibiotic susceptibility of an strain and highlights its putative molecular determinants.