Climate change is expected to increase the frequency and severity of droughts in many regions of the world. Soil health is likely to be negatively impacted by these extreme events. It is therefore important to understand the impact of drought on soil functioning and the delivery of soil-related ecosystem services. This study aimed to assess the resilience and change in physiological status of the microbial community under extreme moisture stress conditions using novel metabolic profiling approaches, namely complex lipids and untargeted primary metabolites. In addition, we used phospholipid fatty acid (PLFA) profiling to identify changes in microbial community structure. Soil samples were collected during a natural, extreme drought event and post-drought from replicated grassland split plots, planted with either deep-rooting Festulolium (cv. AberNiche) or Lolium perenne L. (cv. AberEcho), receiving nitrogen (N) fertiliser loading rates at either 0 or 300 kg N ha−1 yr−1. These plots were split at the start of the drought period, and half of each subplot was irrigated with water throughout the drought period at a rate of 50 mm week−1 to alleviate moisture stress. PLFA analysis revealed a distinct shift in microbial community between drought and post-drought conditions, primarily driven by N loading and water deficit. Complex lipid analysis identified 239 compounds and untargeted analysis of primary metabolites identified 155 compounds. Both soil complex lipids and primary metabolites showed significant changes under drought conditions. Additionally, the irrigated ‘reference’ plots had a significantly higher cumulative greenhouse gas (CO2 and N2O) flux over the period of sampling. Recovery of the microbial lipidome and metabolome to reference plot levels post-drought was rapid (within days). Considerable changes in soil primary metabolomic and lipidomic concentrations shown in this study demonstrate that while soil metabolism was strongly affected by moisture stress, the system (plant and soil) was highly resilient to an intense drought.