Microbial inoculations contribute to reducing agricultural systems’ environmental footprint by supporting sustainable production and regulating climate change. However, the indirect and cascading effects of microbial inoculants through the reshaping of soil microbiome are largely overlooked. By discussing the underlying mechanisms of plant- and soil-based microbial inoculants, we suggest that a key challenge in microbial inoculation is to understand their legacy on indigenous microbial communities and the corresponding impacts on agroecosystem functions and services relevant to climate change. We explain how these legacy effects on the soil microbiome can be understood by building on the mechanisms driving microbial invasions and placing inoculation into the context of ecological succession and community assembly. Overall, we advocate that generalizing field trials to systematically test inoculants’ effectiveness and developing knowledge anchored in the scientific field of biological/microbial invasion are two essential requirements for applying microbial inoculants in agricultural ecosystems to tackle climate change challenges.