Background/Objectives: Gastric cancer (GC) is the fifth leading cause of cancer-related mortality. CLDN18.2 is a tight junction protein, expressed in gastric mucosa and is considered as a novel therapeutic target. Even though CLDN18.2 is associated with various components of the tumor microenvironment and the relation with clinical histopathological parameters has been widely studied, there is no sufficient data on the associations of CLDN18.2 expression and the components of the tumor microenvironment. This systematic review aims to gather and present all available data about the correlation of CLDN 18.2 expression and the tumor microenvironment. Methods: The research questions were systematically formulated using the PICO model to ensure clarity and precision, and the PRISMA flow diagram was constructed to detail the study selection process. Results: Sixteen original articles were retrieved. The major finding of this study was the positive correlation between CLDN18.2 expression and CD8+ T cells, neutrophils and cancer-associated fibroblasts. No correlation was found between CLDN18.2 expression and Tregs and B cells. For the remaining components of the microenvironment, there are contradictory data about their correlation with the expression of CLDN18.2. Conclusions: The tumor microenvironment plays a critical role in cancer progression and needs to be studied more thoroughly.