Wheat production worldwide faces numerous challenges linked to climate change, exponential population growth, nutrient depletion in agricultural soils, and the increasing threat of phytopathogen occurrence. The application of beneficial microorganisms is a promising strategy for crop management as it favorizes nutrient uptake, improves soil fertility, and increases plant resilience. Therefore, this approach facilitates the transition to more sustainable agricultural practices while reducing the dependence on agrochemicals. The valuable beneficial impacts of bioinoculant application include the enrichment of agricultural soils’ ecosystems by restoring microbial populations and interactions that have been lost through the years due to decades of intensive agricultural practices and the massive application of pesticides. Furthermore, beneficial microorganisms constitute a remarkable tool for combating biotic threats, specifically fungal pathogens, whose proliferation and emergence are predicted to increase due to global warming. To optimize their beneficial impact, bioinoculant development requires an extensive study of microbial interactions with plants and their surrounding ecosystem, to improve their composition, mode of action, and stability through application. The use of innovative tools, such as omic sciences, facilitates the elucidation of these mechanisms. Finally, bioprospection and bioformulation must be consciously executed to guarantee the application and persistence of adapted microorganisms and/or their bioactive molecules.