Interactions between metals and microbes are critical in geomicrobiology and vital in microbial ecophysiological processes. Methane-oxidizing bacteria (MOB) and ammonia-oxidizing microorganisms (AOM) are key members in aerobic environments to start the C and N cycles. Ammonia and methane are firstly oxidized by copper-binding metalloproteins, monooxygenases, and diverse iron and copper-containing enzymes that contribute to electron transportation in the energy gain pathway, which is evolutionally connected between MOB and AOM. In this review, we summarized recently updated insight into the diverse physiological pathway of aerobic ammonia and methane oxidation of different MOB and AOM groups and compared the metabolic diversity mediated by different metalloenzymes. The elevation of iron and copper concentrations in ecosystems would be critical in the activity and growth of MOB and AOM, the outcome of which can eventually influence the global C and N cycles. Therefore, we also described the impact of various concentrations of metal compounds on the physiology of MOB and AOM. This review study could give a fundamental strategy to control MOB and AOM in diverse ecosystems because they are significantly related to climate change, eutrophication, and the remediation of contaminated sites for detoxifying pollutants.