Exophiala dermatitidis, a polyextremotolerant black yeast, thrives in diverse natural and human-made environments. Additionally, it is an opportunistic pathogen, capable of infecting immunocompromised individuals, particularly causing neurotropic infections. This study examined 41 E. dermatitidis strains from diverse environments, investigating their growth under different temperatures, NaCl concentrations, and pH levels. Optimal growth occurred at 28 °C, with large variations among strains at other temperatures, from 4 to 42 °C. Growth was enhanced at 5% NaCl, though strains also grew at 10% and 17% NaCl. Growth varied across different pH levels, from pH 2.5 to 12.5. Most strains showed the highest biofilm formation at 37 °C, α- and γ-hemolysis and resistance to antifungal agents. Better growth was detected on neurotransmitters than on (poly)aromatic compounds. High-throughput metabolic analyses revealed consistent oxidation patterns across 94 carbon sources in five selected strains. Genomic analysis revealed a diverse repertoire of carbohydrate-active enzymes and pathways for degrading polyaromatic hydrocarbons and neurotransmitters. Melanin biosynthesis inhibitor tricyclazole minimally affected E. dermatitidis growth under stress, but induced morphological changes in some cases. This study underscores E. dermatitidis' urban extremophilic nature, with high resilience, metabolic adaptability, and potential for heightened pathogenicity in evolving global conditions.