Abstract: Climate change is exacerbating the imbalance of the water circulation and the water resource crisis, posing a severe threat to groundwater systems. Microorganisms play a central role in regulating material recycling and energy fluxes in groundwater system. Understanding the interplay of biotic and abiotic drivers in subterranean ecosystems is required to anticipate effects of climate change on the sustainability of groundwater resources. Here, this review systematically synthesizes the responses of microbial communities to individual and multiple global change factors, including warming, altered precipitation, seawater intrusion, and organic matter input. It is well documented that a change in temperature affects microbial community composition and food web by altering microbial metabolic rates, enzyme activities, and gas solubility. Prolonged drought results in the decreased water retention capacity of soils and groundwater recharge. The associated formation of cracks could lead to stronger seepage water pulses, which were shown to be an important driver in microbial communities in groundwater. Sometimes bacteria can survive in a dormant state, while fungi show stronger drought tolerance. In case of heavy precipitation, it significantly increased groundwater recharge and raised groundwater level. At the same time, precipitation drives the evolution of groundwater microbiome by altering physical properties, dissolved organic carbon concentrations, and nitrate concentrations. Seawater intrusion promotes marine microorganisms to enter the aquifers, which impacts microbial-mediated processes involved in the cycling of carbon, nitrogen, sulfur, and other substances. Furthermore, inputs and variations in organic matter can induce the directional succession of microbial communities, which presents a coupling effect with the migration and transformation of pollutants to further regulate the efficiency of pollutant degradation. Based on high throughput sequencing, stable isotope probing, and numerical modeling, current studies have explored the response characteristics of microorganisms to climate change. However, significant gaps still exist in understanding microbial response mechanisms and predictions of model. Thus, prospective works are urgently needed to deepen mechanistic understanding and develop high-precision predictive models, further providing scientific support for groundwater resources protection and ecological restoration.