Soil microbes, as intermediaries in plant-soil interactions, are closely linked to plant health in grassland ecosystems. In recent years, varying degrees of degradation have been observed in the alpine grasslands of the Qinghai-Tibet Plateau (QTP). Addressing grassland degradation, particularly under the influence of climate change, poses a global challenge. Understanding the factors driving grassland degradation on the QTP and developing appropriate mitigation measures is essential for the future sustainability of this fragile ecosystem. In this review, we discuss the environmental and anthropogenic factors affecting grassland degradation and the corresponding impacts on soil microbe community structure. We summarize the current research on the microbiome of the QTP, in particular the effect of vegetation, climate change, grazing, and land use, respectively on the alpine grassland microbiome. The results of these studies indicate that microbially mediated soil bioprocesses are important drivers of grassland ecosystem functional recovery. Therefore, a thorough understanding of the spatial distribution characteristics of the soil microbiome in alpine grasslands is required, and this necessitates an integrated approach in which the interactions among climatic factors, vegetation characteristics, and human activities are evaluated. Additionally, we assess and summarise current technological developments and prospects for applying soil microbiome technologies in sustainable agriculture, including: (i) single-strain inoculation, and (ii) inoculation of synthetic microbial communities, (iii) microbial community transplantation. Grassland restoration projects should be carried out with the understanding that each restoration measure has a unique effect on the soil microbial activity. We propose that the sustainable development of alpine grassland ecosystems can be achieved by adopting advanced microbiome technologies and integrating microbe-based sustainable agricultural practices to maximise grassland biomass, increase soil carbon, and optimise soil nutrient cycling.