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Mercury (Hg) pollution is a global public health concern because of its adverse effects on the environment and health. Single-nucleotide polymorphisms (SNPs) have been associated with Hg levels and outcomes. The aim of this review was to describe the research and discuss the evidence on the genetic susceptibility of Hg-exposed individuals to the development of neurocognitive disorders. A systematic review was performed to identify the genes/SNPs associated with Hg toxicokinetics and that, therefore, affect neurological function in exposed populations. Observational and experimental studies were identified by screening three databases. Thirteen articles were included (quality score 82–100%) and 8124 individuals were evaluated. Hg exposure was mainly fish consumption (77%) and, in 31% of the studies, the Hg levels exceeded the reference limits. Genetic susceptibility to higher Hg levels and neurotoxicity risk in Hg poisoning were associated with eight (<i>ALAD</i> rs1800435, <i>CYP3A4</i> rs2740574, <i>CYP3A5</i> rs776746, <i>CYP3A7</i> rs2257401, <i>GSTP1</i> rs1695, <i>MT1A</i> rs8052394, <i>MT1M</i> rs2270836, and <i>MT4</i> rs11643815) and three (<i>MT1A</i> rs8052394, <i>MT1M</i> rs2270837, and <i>MT2A</i> rs10636) SNPs, respectively, and rs8052394 was associated with both outcomes. The <i>MT1A</i> rs8052394 SNP may be used as a susceptibility biomarker to identify individuals at greater risk for higher Hg levels and the development of neurocognitive disorders in metal-exposed populations.