Malaria is a potentially fatal disease caused by plasmodium parasites transmitted to humans by female Anopheles mosquitoes. Children under the age of five and pregnant women have a higher susceptibility to malaria. Sub-Saharan Africa accounts for 95% of all cases and deaths from the disease. Plasmodium falciparum is the most virulent among the five known human malaria parasites. Effective antimalarial medications that target several stages of the parasite's life cycle are Quinoline, Antifolates, and Artemisinin and its derivatives. Antimalarial medication resistance is a significant challenge to the battle against malaria since it can result in failure of treatment, more significant morbidity and mortality, higher healthcare expenses, and the potential spread of the disease. The propagation of drug resistance in malaria is influenced by several critical factors, including poor adherence to treatment protocols, inappropriate dosing regimens, and the distribution of substandard or counterfeit drugs that lack sufficient concentrations of active ingredients. These conditions create a selective environment where resistant strains of plasmodium thrive. Resistance in malaria parasites arises through diverse molecular mechanisms, such as genetic mutations that alter the drug target site, gene amplification that increases the expression of resistance-conferring genes, drug efflux that expels antimalarial compounds, and enzymatic systems that degrade or chemically modify the drugs, reducing their efficacy. These adaptive strategies enable the parasite to survive drug exposure and efforts to control and eliminate malaria. Contemporary approaches to malaria drug resistance mitigation thus include omics-based techniques, immunotherapy, drug repurposing, identification of new drug targets, synthesis of selective inhibitors, and identification of resistance reversal agents.