Improving phytoremediation efficiency in lead (Pb) contaminated soil through either bacterial or fungal inoculants have extensively been studied with different successes and limitations. In this study, co-application of bacteria and fungi have been investigated for development of an integrated phytoremediation system (IPS) for efficient Pb removal and restoration of soil microbial and enzymatic activities in degraded soil. For this purpose, Pb tolerant bacterial and fungal strains were firstly analyzed for antifungal and antibacterial activities through disc diffusion method. Afterwards, the co-inoculation studies were performed to investigate the effects on phytoavailability and uptake of Pb by Pelargonium hortorum through soil incubation and pot culture experiments, respectively. Results indicated significant (p < 0.05) antibacterial activity of Mucor spp. against bacterial species (Klebsiella variicola and K. quasipneumoniae). The highest significant increase in extractable Pb fraction (5.0–folds) was observed when soil was co-inoculated with Aspergillus flavus + Microbacterium paraoxydans compared to the control soil (un-inoculated soil) at 2000 mg Pb kg−1 concentration. Similarly, uptake results also indicated significantly higher Pb uptake in plants inoculated with A. flavus + M. paraoxydans. Soil microbial results indicated significant decrease in microbial health indicators and enzymatic activities with increasing Pb concentration and exposure time, as compared to control soil. A relatively severe decline was observed in soil respiration and dehydrogenase (DEH) activities by 2.8– and 2.5–folds, respectively at 2000 mg Pb kg−1 of soil. The optimized IPS was effective for restoring enzymatic activities in Pb contaminated soil and could be applied for sustainable restoration of Pb contaminated soil.