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Neoscytalidium dimidiatumand Bipolarisspecies are fungal plant pathogens that have been reported to cause human diseases. Recently, we have isolated numerous N. dimidiatumand Bipolarisspecies from the skin scrapings and nails of different patients. In this work, we have sequenced the genome of one strain of N. dimidiatum. The sequenced genome was compared to that of a previously reported Bipolaris papendorfiigenome for a better understanding of their complex lifestyle and broad host-range pathogenicity. Both N. dimidiatumUM 880 (~ 43 Mb) and B. papendorfiiUM 226 (~ 33 Mb) genomes include 11,015–12,320 putative coding DNA sequences, of which 0.51–2.49% are predicted transposable elements. Analysis of secondary metabolism gene clusters revealed several genes involved in melanin biosynthesis and iron uptake. The arsenal of CAZymes related to plants pathogenicity is comparable between the species, including genes involved in hemicellulose and pectin decomposition. Several important gene encoding keratinolytic peptidases were identified in N. dimidiatumand B. papendorfii, reflecting their potential pathogenic role in causing skin and nail infections. In this study, additional information on the metabolic features of these two species, such as nutritional profiling, pH tolerance, and osmotolerant, are revealed. The genomic characterization of N. dimidiatumand B. papendorfiiprovides the basis for the future functional studies to gain further insights as to what makes these fungi persist in plants and why they are pathogenic to humans.