Nanoparticles (NPs) application in soil as nano-fertilizers to increase crop yield is getting attention due to their higher efficiency and less environmental risks. This study investigated the interactive effects of variable titanium dioxide nanoparticles (TiO2-NPs) levels (0, 30, 50 and 100 mg kg−1) superimposed to phosphorus (P) fertilizer application in soil at the rates of 0, 25 and 50 mg kg−1 on wheat crop. Physiological parameters of plants, their antioxidant enzymes activities (SOD, POD), and contents of crude protein, H2O2, MDA and metals/nutrients (Al, Ca, Mg, Fe, Zn and Cu) were measured. Data on physiological traits revealed that application of 50 mg kg−1 of TiO2-NPs without P fertilizer significantly enhanced the root and shoot length by 63 and 26%, respectively. Increased contents of nutrients in the shoots, viz., Ca (316%), Cu (296%), Al (171%) and Mg (187%) with 50 mg kg−1 TiO2-NPs treatment reflected improvement in crop growth and grain quality. Furthermore, P contents in plant tissues were raised up to 56% with 50 mg kg−1 of TiO2-NPs even in the absence of P fertilizer. In the soil, concentration of phytoavailable P was significantly increased up to 63.3% in the presence of 50 mg kg−1 TiO2-NPs as compared to control. Contents of crude protein in grain were also enhanced by 22.8% (at P50) and 17.4% (at P25) with 50 mg kg−1 TiO2-NPs application. Along with P application, TiO2-NPs triggered the activities of SOD (2.06–33.97%) and POD (up to 13.19%), and H2O2 production (50.6–138.8%). However, MDA contents were not elevated significantly at any level of TiO2-NPs, and remained at par with control. It was noteworthy that highest level of TiO2-NPs, viz., 100 mg kg−1 exhibited plant and nutrients response lower than that with 50 mg kg−1. Further, TiO2-NPs triggered the bioavailability of micronutrient heavy metals (Zn, Cu and Fe) and Al, which could have toxicity at higher concentrations. These results suggested that TiO2-NPs might have some affinities with phosphate compounds and metal ions in the soil to bring them in soluble form, which enhanced their bioavailability. Although it improved the crop yield and quality, but toxic or negative impact of TiO2-NPs was also apparent at higher dose. Therefore, investigations on the potential interactions of NPs with other nutrients and toxic metals are needed to enhance our understanding for the safer application of nano-fertilizer.