Xylella fastidiosa (Xf) causing Pierce’s Disease (PD) of grapevine is known to associate with endophytes (microbiome) during infection and pathogenicity development. The increase of Xf genetic resources in online databases, along with improved sequencing and genetic analysis technology, has provided a framework to study the PD microbiome. In this study, DNA was extracted from a PD symptomatic grapevine inoculated with Xf strain Stag’s Leap in greenhouse (Greenhouse Grape - GG), and a PD symptomatic grapevine from a vineyard in Bakersfield, CA (Field Grape - FG). Illumina HiSeq was used on GG and generated 190 M 100-bp short sequence reads. Illumina MiSeq was used on FG and generated 39 M 250-bp short sequence reads. Percentages of Xf reads were 1.7 for GG, and 0.5 for FG. Genomic variations of Xf under different conditions (field, greenhouse, sampling time) were studied. The microbiomes of GG and FG were analyzed to determine the major taxonomic groups of bacteria and fungi through metagenomic approach with the help of Kaiju software. The most abundant bacterial genera present in GG was Xf. The most abundant bacterial genera present in FG was Paenarthrobacter, with Xf ranking-the third. Many endophytic bacteria such as Enterococcus, Staphylococcus, and Paraburkholderia were observed. These results provide new information on grape microbiome associated with Xf infection under greenhouse and field environment.