Background <p><i>Anopheles albimanus</i>, <i>Anopheles darlingi</i>, <i>Anopheles dirus</i>, and <i>Anopheles punctipennis</i> are key malaria vectors across multiple regions. Insecticide resistance especially to organochlorines poses a major challenge to vector control. While knockdown resistance (<i>kdr</i>) mutations are a well-known resistance mechanism, evidence in these species remains inconclusive. This study systematically reviewed the presence of <i>kdr</i> mutations associated with organochlorine resistance in these four <i>Anopheles</i> species.</p> Methods <p>A systematic review was conducted in accordance with PRISMA guidelines. Six international databases PubMed, Web of Science, Scopus, Cochrane Library, ScienceDirect, and Google Scholar were searched up to June 2024. Keywords included “kdr mutation,” “organochlorine resistance,” “malaria vectors,” and related terms. Inclusion criteria focused on studies examining <i>kdr</i> mutations and organochlorine resistance in the four target <i>Anopheles</i> species. The quality of studies was assessed using the STROBE checklist. Five studies met all eligibility criteria and were included.</p> Results <p>Across the five included studies, no <i>kdr</i> mutations (particularly at codons 1010, 1013, or 1014 in the VGSC gene) were identified in any of the four species. Resistance observed in these mosquitoes was attributed primarily to metabolic mechanisms, including elevated activity of mixed-function oxidases (MFO) and non-specific esterases (NSE), rather than target-site insensitivity.</p> Conclusion <p>Current evidence indicates that <i>kdr</i> mutations do not contribute to organochlorine resistance in <i>An. albimanus</i>, <i>An. darlingi</i>, <i>An. dirus</i>, or <i>An. punctipennis</i>. Metabolic and behavioural resistance mechanisms appear to play a larger role. Given the limited number of studies and gene regions analysed, further research with broader genetic screening is essential to fully understand resistance dynamics in these vectors.</p>