Water stress or soil salinity is considered the major environmental factor affecting plant growth. When both challenges are present, the soil becomes infertile, limiting plant productivity. In this work a field experiment was conducted during the summer 2019 and 2020 seasons to evaluate whether plant growth-promoting microbes (PGPMs) and nanoparticles (Si-ZnNPs) have the potential to maintain soybean growth, productivity, and seed quality under different watering intervals (every 11 (IW0), 15 (IW1) and 19 (IW2) days) in salt-affected soil. The most extended watering intervals (IW1 and IW2) caused significant increases in Na+ content, and oxidative damage indicators (malondialdehyde (MDA) and electrolyte leakage (EL%)), which led to significant reductions in soybean relative water content (RWC), stomatal conductance, leaf K+, photosynthetic pigments, soluble protein. Subsequently reduced the vegetative growth (root length, nodules dry weight, and total leaves area) and seeds yield. However, there was an enhancement in the antioxidants defense system (enzymatic and non-enzymatic antioxidant). The individual application of PGPMs or Si-ZnNPs significantly improved leaf K+ content, photosynthetic pigments, RWC, stomatal conductance, total soluble sugars (TSS), CAT, POD, SOD, number of pods plant−1, and seed yield through decreasing the leaf Na+ content, MDA, and EL%. The combined application of PGPMs and Si-ZnNPs minimized the adverse impact of water stress and soil salinity by maximizing the root length, heavier nodules dry weight, leaves area, TSS and the activity of antioxidant enzymes, which resulted in higher soybean growth and productivity, which suggests their use under harsh growing conditions.