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Emerging and uncommon <i>Candida</i> species have been reported as an increasing cause of invasive <i>Candida</i> infections (ICI). We aim to systematize the global epidemiology associated with emergent uncommon <i>Candida</i> species responsible for invasive infections in adult patients. A systematic review (from 1 January 2001 to 28 February 2023) regarding epidemiological, clinical, and microbiological data associated to invasive <i>Candida</i> infections by uncommon <i>Candida</i> spp. were collected. In total, 1567 publications were identified, and 36 were selected according to inclusion criteria (45 cases). The chosen studies covered: <i>C. auris</i> (<i>n</i> = 21), <i>C. haemulonii</i> (<i>n</i> = 6), <i>C. fermentati</i> (<i>n</i> = 4), <i>C. kefyr</i> (<i>n</i> = 4), <i>C. norvegensis</i> (<i>n</i> = 3), <i>C. nivariensis</i> (<i>n</i> = 3), <i>C. bracarensis</i> (<i>n</i> = 1), <i>C. duobushaemulonii</i> (<i>n</i> = 1), <i>C. blankii</i> (<i>n</i> = 1), and <i>C. khanbhai</i> (<i>n</i> = 1). Over the recent years, there has been an increase in the number of invasive infections caused by uncommon <i>Candida</i> spp. Asia and Europe are the continents with the most reported cases. The challenges in strain identification and antifungal susceptibility interpretation were significant. The absence of clinical breakpoints for the susceptibility profile determination for uncommon <i>Candida</i> spp. makes interpretation and treatment options a clinical challenge. It is crucial that we focus on new and accessible microbiology techniques to make fast and accurate diagnostics and treatments.