Aims Manila clam (Ruditapes philippinarum) is one of the most popular seafood in Korea, owing to their unique taste and nutritional value. This study aimed to disclose the antibiotic and heavy metal resistance characteristics of Aeromonas spp. isolated from marketed Manila clam in Korea. Methods and results A total of 36 Aeromonas spp. strains were isolated and subjected to two tests: an antibiotic disk diffusion test to determine their resistance to antibiotics, and a broth dilution test to determine their resistance to heavy metals. PCR-based amplification was performed to detect the resistance genes. A high level of resistance to ampicillin (100%) and cephalothin (89%) was observed, while 42, 39, 36 and 36% of the isolates were resistant to oxytetracycline, imipenem, nalidixic acid and tetracycline respectively. In addition, among the tested heavy metals, cadmium (Cd) recorded the highest resistance rate (61%), followed by chromium (Cr) (50%), lead (Pb) (47%) and copper (Cu) (37%). However, mercury (Hg) resistance was not observed. PCRs revealed the occurrence of bla(TEM), bla(SHV), bla(CTX-M), qnrS, tetB, tetE, aac(6 ')-Ib, strA-strB and intI1 genes among 100, 31, 31, 78, 78, 89, 25, 50 and 72% of the isolates respectively. Moreover, heavy metal resistance genes, copA, merA and czcA were detected in 25, 47 and 61% of the isolates respectively. Conclusions The results suggest the importance of multi-drug and heavy metal-resistant aeromonads in Manila clam to assess the consumer safety and public health. Significance and Impact of the Study This study is the first to elaborate on the importance of multi-drug and heavy metal-resistant aeromonads in Manila clam. Particularly, the presence of extended-spectrum-beta-lactamase genes and other antibiotic resistance genes intensifies the possible health risks and may complicate therapeutic treatments upon infection, while heavy metal resistance suggests possible heavy metal exposure.