Drought generates a complex scenario worldwide in which agriculture should urgently
be reframed from an integrative point of view. It includes the search for new water
resources and the use of tolerant crops and genotypes, improved irrigation systems,
and other less explored alternatives that are very important, such as biotechnological
tools that may increase the water use efficiency. Currently, a large body of evidence
highlights the role of specific strains in the main microbial rhizosphere groups (arbuscular
mycorrhizal fungi, yeasts, and bacteria) on increasing the drought tolerance of their
host plants through diverse plant growth-promoting (PGP) characteristics. With this
background, it is possible to suggest that the joint use of distinct PGP microbes
could produce positive interactions or additive beneficial effects on their host plants
if their co-inoculation does not generate antagonistic responses. To date, such effects
have only been partially analyzed by using single omics tools, such as genomics, metabolomics,
or proteomics. However, there is a gap of information in the use of multi-omics approaches
to detect interactions between PGP and host plants. This approach must be the next
scale-jump in the study of the interaction of soil-plant-microorganism. In this review,
we analyzed the constraints posed by drought in the framework of an increasing global
demand for plant production, integrating the important role played by the rhizosphere
biota as a PGP agent. Using multi-omics approaches to understand in depth the processes
that occur in plants in the presence of microorganisms can allow us to modulate their
combined use and drive it to increase crop yields, improving production processes
to attend the growing global demand for food.