Plant root-knot disease caused by nematodes is a serious threat to agricultural production worldwide, second only to fungal diseases. Meloidogyne incognita is the most prevalent nematode species among RKN infested vegetables and cash crops. To explore the most potential biocontrol agents for Meloidogyne incognita, this study employed metabolomics and high-throughput sequencing approaches to assess alterations in metabolite profiles and microbial community structures of the rhizosphere soil around tomato (Solanum lycopersicum) roots before and after Meloidogyne incognita infestation. Subsequently, a comprehensive analysis of the metabolome and microbial diversity was conducted to identify differentially accumulated metabolites, microbes, and their correlation with each other. As a result, a total of 51 metabolites and 28 microbial genera exhibited significant differences in abundance between the treatments. Specifically, 27 metabolites were increased in concentration while 24 decreased, and the abundance of 25 bacterial genera and three fungal species was significantly altered. Further analysis revealed that five metabolites, including 5-fluorouridine monophosphate and fusarochromanone, as well as nine microbial genera, such as Bacillus, Streptomyces, and Paenibacillus, exhibited potential correlation with the biocontrol agents. In conclusion, the infestation of tomatoes by M. incognita results in substantial alterations to the metabolite profiles and microbial community structures within the rhizosphere soil. Five of the metabolites and nine microbial genera were identified as potential candidates for biocontrol of M. incognita.