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Simple Summary: Wheat is a vital source of food, and its production is increasingly threatened by drought episodes. Moreover, its cultivation under water deficit situations along with zinc deficient soils is a major concern of declined wheat grain quantity and quality. Drought-linked changes in nutrient use efficiency, photosynthetic mechanisms, and chemical composition of wheat plants ultimately led to poorer harvest. Therefore, we aimed to understand the drought-ameliorating and grain nutritional improving effects in wheat by rhizobacteria (Azospirillum brasilense) and ZnO nanoparticles (NPs) under various growth stage-based drought stress episodes. Rhizobacteria colonized the host plant rhizosphere and provided growth promotion and stress amelioration. ZnO NPs were recognized as a potential water and zinc deficiency alleviator, and general growth promoter by triggering nitrogen metabolism, chlorophyll synthesis, membrane integrity, and grain zinc biofortification activities. Physio-biochemical observations indicated significantly higher positive effects under co-application over the sole use of either microbial or nanomaterials. Based on our research, it was concluded that co-applied Azospirillum brasilense and ZnO NPs generally increase wheat productivity under drought episodes with low operational cost to growers. Further, plausible synergistic physiological enhancement by NPs and rhizobacteria interaction may contribute towards sustainable wheat crop management under abiotic stresses. Drought is a major abiotic factor and affects cereal-based staple food production and reliability in developing countries such as Pakistan. To ensure a sustainable and consistent food supply, holistic production plans involving the integration of several drought mitigation approaches are required. Using a randomized complete block design strategy, we examined the drought-ameliorating characteristics of plant growth-promoting rhizobacteria (PGPR) and nanoparticles (NPs) exclusively or as a combined application (T4) through three stages (D1, D2, and D3) of wheat growth (T1, control). Our field research revealed that Azospirillum brasilense alone (T2) and zinc oxide NPs (T3) improved wheat plant water relations, chlorophyll, proline, phenolics and grain quality, yield, and their allied traits over the stressed treatments. Specifically, the best outcome was observed in the combined treatment of PGPR and ZnO NPs (T4). Interestingly, the combined treatment delivered effective drought mitigation through enhanced levels of antioxidants (15% APX, 27% POD, 35% CAT, 38% PPO and 44% SOD) over controls at the grain-filling stage (GFS, D3 × T1). The 40% improvements were recorded under the combined treatment at GFS over their respective controls. Their combined usage (PGPR and ZnO NPs) was concluded as an effective strategy for building wheat resilience under drought, especially in arid and semi-arid localities. [ABSTRACT FROM AUTHOR]