As a filter feeding bivalve marine organism, oyster is easy to accumulate microorganisms due to its living habits. In this study, oysters from four coastal areas of China were selected as the research objects. The microbie diversity in different samples and the distribution of antibiotic and heavy metal resistance genes in intestinal, gill and muscle were analyzed. Finally, the correlation between resistance genes was compared by correlation analysis. The results showed that:(1) The top five bacteria with microbial content are uncultured Bacteroides, unclassified Bacillus cohn, unclassified Pseudomonas, Vibrio fluvialis and Arcobacter skirrowii, including two types of spoilage bacteria and one type of pathogenic bacteria; (2) In terms of resistance gene types, the detection rate of aminoglycoside args is the highest (84.1%), β-lactam args and quinolone args were the lowest (57.1%). Detected by different tissues and organs of oyster, the detection rate in muscle (65.6%) > gill (59.1%) > intestine (58.4%). Detected from different sample sources, the overall detection rate of GXBH samples is the highest (72.7%), and the overall detection rate of SDWH1 is the lowest (54.5%), and the samples from different sources have no significant difference in the type and abundance of resistance genes. After PCA analysis, it is found that the same sample can be significantly normalized and classified, indicating that the resistance genes in different tissues and organs of the same sample are highly correlated. (3) From the correlation analysis of different resistance genes ARGs and HTGs, CARB and qnrS have the highest correlation, chrR has a great correlation with sulA and mecA, and copA has a certain correlation with all kinds of ARGs, indicating that different types of resistance genes have the possibility of sharing a gene box. From the correlation analysis of samples from different sources, it basically follows the normalized classification of samples from different places of origin. It shows that the breeding environment can affect the distribution of resistance genes in oysters. Through the above studies, the dominant microbial groups in oysters were analyzed, and the correlation between resistance genes and varieties, places of origin, tissues and organs was preliminarily compared, which laid a foundation for further research on the mechanism of resistance.