Irrigation scheduling, coupled with the use of biofertilizers, constitutes an effective management strategy to overcome soil drought. This study aimed to assess the individual and combined effects of three selected biofertilizers—(R) Bacillus sp. and Bacillus subtilis, (M) native arbuscular mycorrhizal fungi, and (C) compost—on Triticum durum L. The agro-physiological and biochemical traits, along with the soil properties, were evaluated under two different water regimes, 100% crop evapotranspiration (ETc) for the well-watered regime and 30% ETc for the drought-stressed regime under field conditions, using a drip irrigation system. Drought stress (DS) led to significant reductions in the biomass, physiological parameters, and biochemical markers. Furthermore, the application of CM and MR significantly boosted the shoot and root dry weight by 137% and 72%, respectively, under DS compared to the control. Moreover, CM and R resulted in a notable increase of 167% and 130% in the grain and straw yield, respectively, under the same conditions. The normalized difference vegetation index showed improved values in the plants inoculated with MR and CMR, respectively, under DS conditions. Additionally, the soil quality was positively influenced by the application of M and/or R and/or C biofertilizers. These findings provide valuable insights into the intricate soil–plant interactions and the beneficial effects of combined biofertilizers in enhancing wheat’s resilience to drought stress.