The indiscriminate use of chemical fertilizers and pesticides has caused considerable environmental damage over the years. However, the growing demand for food in the coming years and decades requires the use of increasingly productive and efficient agriculture. Several studies carried out in recent years have shown how the application of plant growth-promoting microbes (PGPMs) can be a valid substitute for chemical industry products and represent a valid eco-friendly alternative. However, because of the complexity of interactions created with the numerous biotic and abiotic factors (i.e., environment, soil, interactions between microorganisms, etc.), the different formulates often show variable effects. In this review, we analyze the main factors that influence the effectiveness of PGPM applications and some of the applications that make them a useful tool for agroecological transition…