Sustainable agricultural systems based on the application of phyto-friendly bacteria and fungi are increasingly needed to preserve soil fertility and microbial biodiversity, as well as to reduce the use of chemical fertilizers and pesticides. Although there is considerable attention on the potential applications of microbial consortia as biofertilizers and biocontrol agents for crop management, knowledge on the molecular responses modulated in host plants because of these beneficial associations is still incomplete. This review provides an up-to-date overview of the different mechanisms of action triggered by plant-growth-promoting microorganisms (PGPMs) to promote host-plant growth and improve its defense system. In addition, we combined available gene-expression profiling data from tomato roots sampled in the early stages of interaction with Pseudomonas or Trichoderma strains to develop an integrated model that describes the common processes activated by both PGPMs and highlights the host’s different responses to the two microorganisms. All the information gathered will help define new strategies for the selection of crop varieties with a better ability to benefit from the elicitation of microbial inoculants.