Abstract Malaria constitutes a major public health concern in tropical and other malaria-endemic regions. Genetic and non-genetic factors are known to influence the pharmacokinetics and/or pharmacodynamics of drugs including antimalarial drugs resulting in variability in drug responses. This article aimed to update perspectives on pharmacogenomics and also provide an updated appraisal of genetic variability in drug-metabolizing enzymes which alter the disposition of antimalarial drugs causing variations in treatment outcomes. Important literature databases such as Elsevier, IEEExplore, Pubmed, Scopus, Web of Science, Google Scholar, ProQuest, ScienceDirect, and BioMed Central were selected based on the quality, extant content, and broad area of the discipline. The specific keywords related to the study were identified and used for the study purposely to identify related works. Advances in genetic research have facilitated the identification of Single Nucleotide Polymorphisms (SNPs) that alter the activity of drug-metabolizing enzymes that metabolize most antimalarial drugs. There is an association between isoforms of CYP450 gene variants and the efficacy of some antimalarial drugs, and this may be applied to the optimization of malarial therapy. Although identification of cytochrome P450 (CYP450) gene variants can be used for personalization of malaria treatment, several challenges are encountered in this process but some resources provide education and guidelines on how to use the pharmacogenetic results of specific drugs.