Soils in the Botevgrad Valley, Western Bulgaria, have been exposed to long-term anthropogenic pressure arising from industrial emissions of the Kremikovtsi metallurgical complex, intensive agriculture, and expanding urbanisation. These drivers have contributed to the accumulation of heavy metals and the alteration of soil fertility, raising concerns about the long-term ecological stability of the valley ecosystem. Despite the significance of the region, information on the microbiological and enzymatic characteristics of these soils as sensitive bioindicators remains limited. The present study aimed to examine how key physicochemical factors influence these enzymes and to evaluate their potential for assessing soil quality and resilience under anthropogenic impact. Representative soil samples were taken following a spatial grid covering agricultural, forest, and semi-urban sites, with agricultural soil dominating. Basic soil parameters (pH, humus, moisture, nutrients) and trace elements (Pb, Mn, Cu, Fe, Zn, Cd) were determined, while microbial composition and the activities of cellulase and catalase were analysed by conventional microbiological and enzymatic methods. Correlation and multiple regression analyses were applied to identify the main dependencies and independent predictors. Lead concentrations exceeded the permissible levels at two sites, while cadmium and copper were elevated at one. Cellulase activity was generally high, indicating active microbial decomposition, and correlated positively with soil moisture, total nitrogen, potassium, and microbial abundance, whereas Pb and Mn exerted pronounced inhibitory effects. Catalase activity reached maximum values in the Eutric Fluvisols and minimum values in the Pb- and Cu-enriched Skeletic Phaeozems. It correlated positively with iron, humus, and available phosphorus, showing weaker positive relationships with microbial indicators. Regression analysis confirmed Pb as the strongest negative predictor of both enzymes, while humus, phosphorus, and pH showed significant positive effects on catalase. Iron played an indirect stimulatory role by associating with organic matter and nutrients. The integration of correlation and regression analyses identified Pb and Mn as the main inhibitors of enzymatic activity, while soil nutrients, pH, and moisture stimulated microbial processes. The persistence of relatively high catalase and cellulase activities, even under contamination, indicated the presence of resilient microbial communities and a potential for natural self-purification. Overall, the findings confirm that cellulase and catalase are reliable bioindicators for evaluating soil quality, fertility, and resilience in valley ecosystems under anthropogenic stress, providing a scientific basis for sustainable land-use management and environmental restoration strategies.