The use of ecofriendly strategies, such as the use of Plant Growth Promoting Bacteria, to improve the yield and quality of crops has become necessary to satisfy the growing demand of food and to avoid the use of chemical fertilizers and pesticides. In this study, we report the effects of an innovative microbial inoculation technique, namely Effective Microorganisms (EM), compared with traditional approaches, on productivity and nutritional aspect of four tomato varieties: Brandywine, Corbarino Giallo, S. Marzano Cirio 3, S. Marzano Antico. Results showed an increase of plant productivity as well as an enhanced antioxidant activity mainly in San Marzano Antico and Brandywine varieties treated with EM technology. Moreover, the polyphenol and carotenoid contents also changed, in response to the plant treatments. In conclusion, the application of EM^® technology in agriculture could represent a very promising strategy in agricultural sustainability.