Against the backdrop of global population growth and environmental changes, intensive agriculture under continuous cropping systems has exacerbated the frequent occurrence of soil-borne diseases and continuous cropping obstacles, while traditional chemical control methods are increasingly incompatible with the demands of green and sustainable agricultural development. Healthy soil serves as the foundation for crop disease resistance and stable productivity. As the core microdomain for “soil-plant-microbe” interactions, the rhizosphere relies on the bidirectional dynamic and synergistic regulation between the rhizosphere microbiome and root exudates as the core intrinsic mechanism of soil-borne disease defense. Root exudates directionally regulate the functional gene expression of the rhizosphere microbiome through specific signaling molecules. This can either drive the enrichment of beneficial microbial communities and the activation of disease-resistant functions, or selectively enrich pathogens to form malignant interactions under continuous cropping conditions. In return, the rhizosphere microbiome feeds back to plant roots via metabolites, optimizing the composition and secretion rhythm of root exudates, and together they constitute a dynamic balance network of “beneficial interaction-malignant interaction”. Soil physicochemical properties such as texture, pH, and organic matter content play key mediating roles in this process, directly affecting interaction efficiency and disease control effects. This review systematically summarizes the core pathways of their synergistic disease resistance: root exudates directly inhibit pathogens or directionally recruit beneficial microorganisms through “concentration/type-dependent” mechanisms; the rhizosphere microbiome suppresses diseases through multiple pathways, including direct antagonism, nutrient competition, immune activation, and autotoxin degradation. On this basis, the paper synthesizes technological innovations such as the construction of synthetic microbial communities, optimization of agricultural practices, gene editing, and synthetic biology, and analyzes the current bottlenecks in the field promotion of these technologies. The study proposes that future research should focus on constructing a “soil type-metabolite-receptor-gene” precision regulation network and establishing a “short term-medium term-long term” three-level ecological risk assessment system. This study aims to provide theoretical support and technical pathways for resolving the contradiction between crop productivity guarantee and ecological security under continuous cropping obstacles, while offering references for the synergistic inhibition of other types of plant diseases through rhizosphere microecological regulation.