The intricate involvement of Rho GTPases in a multitude of human malignancies and their diverse array of biological functions has garnered substantial attention within the scientific community. However, their expression pattern and potential role in gastric cancer (GC) remain unclear. In this study, we successfully identified two distinct subtypes associated with Rho GTPase-related gene (RGG) through consensus clustering analysis, which exhibited significant disparities in overall survival and the tumor microenvironment. Subsequently, an extensively validated risk model termed RGGscore was meticulously constructed to prognosticate the outcomes of GC patients. This model was further assessed and validated using an external cohort. Notably, the high RGGscore group was indicative of a poorer prognosis. Univariate and multivariate Cox regression analyses unveiled the RGGscore as an autonomous prognostic indicator for GC patients. Subsequent external validation, utilizing two cohorts of patients who underwent immunotherapy, demonstrated a significant correlation between a low RGGscore and improved response to immunotherapy. Additionally, the expression levels of three genes associated with RGGscore were examined using qRT-PCR. Taken together, a pioneering RGGscore model has been successfully established, showcasing its potential efficacy in offering valuable therapeutic guidance for GC.