Our findings provide a translational framework: (1) ARID1A methylation status combined with PD-L1 expression may jointly stratify GC patients for ICB therapy, pending clinical validation; (2) 5-aza-CdR enhances PD-1 inhibition efficacy in ARID1A-silenced GC models, suggesting epigenetic priming may overcome immune resistance; and (3) Methylation-guided stratification proposes a biomarker hypothesis for triple combination therapy (5-aza-CdR + ICB + AKT inhibitor). Here, AKT1 is linked to gastric cancer.