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Pharmacoresistance is present in at least one\u2010third of patients with MTLE with HS (MTLE+HS). Several hypotheses have been proposed to explain the mechanisms of pharmacoresistance in epilepsy, including the effect of genetic and molecular factors. In recent years, the increased knowledge generated by high\u2010throughput omic technologies has significantly improved the power of molecular genetic studies to discover new mechanisms leading to disease and response to treatment. In this review, we present and discuss the contribution of different omic modalities to understand the basic mechanisms determining pharmacoresistance in patients with MTLE+HS. We provide an overview and a critical discussion of the findings, limitations, new approaches, and future directions of these studies to improve the understanding of pharmacoresistance in MTLE+HS. However, it is important to point out that, as with other complex traits, pharmacoresistance to anti\u2010seizure medications is likely a multifactorial condition in which gene\u2010gene and gene\u2010environment interactions play an important role. Thus, studies using multidimensional approaches are more likely to unravel these intricate biological processes.<\/jats:p>","DOI":"10.1002\/epi4.12536","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T11:39:32Z","timestamp":1630928372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multi\u2010omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy"],"prefix":"10.1002","volume":"7","author":[{"given":"Estela M.","family":"Bruxel","sequence":"first","affiliation":[{"name":"Departments of Translational Medicine School of Medical Sciences University of Campinas (UNICAMP) Campinas Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN) Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda M.","family":"do Canto","sequence":"additional","affiliation":[{"name":"Departments of Translational Medicine School of Medical Sciences University of Campinas (UNICAMP) Campinas Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN) Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle C. 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