Heavy metal pollution in agricultural fields is a serious health concern because of the high bioavailability and persistent toxicity of heavy metals. Much progress has recently been made with respect to elucidating the impacts of climate change (e.g., elevated atmospheric CO₂ concentrations) on the environmental behavior of heavy metal pollutants and the associated ecological and health risks. The microbiological responses to elevated CO₂ levels are primarily mediated by the C balance in agricultural activities; however, the underlying mechanisms involved in plant–soil–microbe interactions under heavy metal stress are still unclear. Thus, in this study, the challenges and perspectives with regard to controlling heavy metal pollution and optimizing crop yields while reducing greenhouse emissions in agricultural ecosystems responsive to elevated CO₂ levels are discussed. Considering the integrated benefits of intensive agriculture and food security under a future changing climate, the summarized findings provided in this study may help to develop applicable remediation approaches for sustainably managing heavy metal polluted soils.