The physiological impacts and interactions of ARGs abundance, microcystin synthetase genes expression, GO, and M. aeruginosa in synthetic wastewater were investigated. The results demonstrated that the absolute abundance of sul1, sul2, tetW, and tetM in synthetic wastewater dramatically increased to 365.2%, 427.1%, 375.2%, and 231.7%, respectively, when the GO concentration was 0.01 mg/L. Even more interesting is that the sum gene copy numbers of mcyA-J also increased to 243.2%. The appearance of GO made the significant correlation exist between ARGs abundance and mcyA-J expression. Furthermore, M. aeruginosa displayed better photosynthetic performance and more MCs production at 0.01 mg/L GO. There were 65 pairs of positive correlations between the intracellular differential metabolites of M. aeruginosa and the abundance of sul1, sul2, tetM, and tetW with various GO concentrations. The GO will impact the metabolites and metabolic pathway in M. aeruginosa. The metabolic changes impacted the ARGs, microcystin synthetase genes, and physiological characters in algal cells. Furthermore, there were complex correlations among sul1, sul2, tetM, tetW, mcyA-J, MCs, photosynthetic performance parameters, and ROS. The different concentration of GO will aggravate the hazards of M. aeruginosa by promoting the expression of mcyA-J, producing more MCs, simultaneously, it may cause the spread of ARGs.