The development of resistance to antimalarial drugs has severely threatened global efforts to control and eliminate malaria. Immediate measures addressing the spread of resistance are needed to reduce the current and future burden of this disease. Molecular monitoring of polymorphisms in genetic markers associated with drug resistance can aid in vivo clinical trials determine the efficacy of antimalarial drugs. To determine the genetic heterogeneity of the prevailing malaria parasites in Palawan, where most of the cases are reported over the years, drug resistance genotyping was performed in Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) samples. Known polymorphisms in genes associated with chloroquine and sulfadoxine-pyrimethamine (SP) resistance of P. falciparum (pfmdr1 N86Y184, pfcrt C72V73M74N75K76, pfdhfr N51C59S108, pfdhps S436A437K540A581A613) and P. vivax (pvmdr1 Y976F1076, pvdhfr I13P33F57S58T61S117I173, pvdhps S382A383K512A553) were observed. A total of 165 Pf and 59 Pv positive samples were genotyped using nested PCR. Molecular characterization of genes associated with chloroquine resistance suggests that all Pf parasites harbored wild type alleles in pfmdr1 and pfcrt genes whereas 96% of the Pv samples carried single mutation 1076L in the pvmdr1 gene. For SP resistance, majority of the Pf samples had wild type haplotype in the pfdhfr gene while single mutation F436A437K540A581A613 was most observed in the pfdhps gene. In addition, analysis of Pv markers dhfr and dhps revealed that majority of the Pv isolates harbored double mutation I13P33F57R58T61N117I173 and wild type alleles, respectively. With observed differences in spatial patterns, these genetic profiles provide useful information on the prevalence of markers for drug resistance for the two most prevalent malaria species in the country. Continued monitoring might warn against its possible emergence which might hamper malaria elimination in the Philippines.