Plant health is strongly influenced by microorganisms living within and near plant tissues. In agroecosystems, crops dynamically experience a diverse array of biotic and abiotic stresses (e.g., drought, diseases, parasitic weeds) causing negative impacts on crop performance and productivity. In this lecture, I will review the complexity of soil and plant-associated microbiomes and explore innovative strategies to manipulate and activate beneficial microbial taxa and functions at the plant-soil interface. A focus will be given to recent research findings that illustrate the role of plant-protective microbiomes in controlling soil-borne diseases and suppressing the germination of one of the most important parasitic weeds Striga impacting the livelihood of millions of people in sub-Saharan Africa. I will end this lecture by providing a new perspective on strategies to effectively engineer agricultural microbiomes and harness microbial functions to promote sustainability and crop security with implications across diverse agroecosystems.