Gastric cancer (GC) remains a major global health challenge, characterized by a complex tumor microenvironment (TME) that significantly influences disease progression and therapeutic outcomes. This study focuses on TREM2(+) lipid-associated macrophages (LAM) and cancer-associated fibroblasts (CAFs) in modulating the GC microenvironment. Utilizing advanced single-cell RNA sequencing and bulk RNA analyses, we elucidated the interactive mechanisms through which CAFs enhance the immunosuppressive capabilities of TREM2(+) LAMs via the CXCL12-CXCR4 signaling axis. Our findings reveal that this interaction facilitates tumor proliferation and inhibits apoptotic processes in GC cells. In vitro experiments confirmed the modulation of this pathway significantly affects tumor cell viability and invasiveness, underscoring the critical roles of these cellular interactions in promoting GC progression. These insights present TREM2(+) LAMs and CAFs as potential therapeutic targets, offering new avenues for improving outcomes in GC treatment.