During the ongoing studies designed to examine the fungal diversity present within the abandoned and flooded Escádia Grande gold mine (Góis, Portugal), we repeatedly isolated several specimens belonging to a Penicillium species. Molecular phylogenetic analysis, coupled with morphological observations, positioned this fungus within subgen. Penicillium sect. Paradoxa, series Atramentosa, pinpointing its identity as Penicillium mexicanum (the first record for mining soils and the country). Given the limited research conducted on Penicillia isolated from similar environments, the species genome was sequenced utilizing the Oxford Nanopore® MinION™ methodology and studied through bioinformatic analysis. The obtained genome has a size of 29.62 Mb, containing a 47.72% GC content, 10,156 genes, with 44 rRNAs and 178 tRNAs/tmRNAs, providing the first genomic resource for this microorganism. Bioinformatic analysis allowed us to identify multiple genomic traits that can contribute towards this species survival in these extreme environments, including the presence of high levels of major facilitator transporters (MFS), Zn (2)-C6 fungal-type DNA-binding domains, P-loop containing nucleoside triphosphate hydrolases, specific fungal transcription factors and sugar transporters. Furthermore, putative advantageous metabolic traits, such as methylotrophy, assimilatory nitrate and sulfate reduction abilities, were also detected. In addition, the results also highlighted a strong genomic and metabolic organization and investment towards arsenic detoxification (transport and oxidation). Lastly, thirty-two putative biosynthetic gene clusters were predicted, including some with high similarity values to monascorubrin, nidulanin A, histidyltryptophanyldiketopiperazine/dehydrohistidyltryptophanyldiketopiperazine/roquefortine D/roquefortine C/glandicoline A/glandicoline B/meleagrine, YWA1 and choline. Overall, this study expands the current Penicillia knowledge from mining environments while also enhancing our understanding regarding fungal arsenic resistance.