The article reviews the regulatory roles of the WNT/β-catenin signaling pathway on the PD-1/PD-L1 axis in the tumor immune ecosystem, discussing its impact on immune checkpoint inhibitor (ICI) therapy responses. Overactive WNT/β-catenin signaling is associated with low immune infiltration, T cell exclusion, and increased regulatory T cells (Tregs) in tumors. It also induces the expression of PD-L1 on tumor cells and promotes PD-1 upregulation, which can lead to resistance to ICI therapy. The review highlights the potential of combining WNT/β-catenin inhibitors with anti-PD-(L)1 agents as a promising regimen to enhance anti-tumor immunity. Key mechanisms include the suppression of Treg cells, increased CD8+ T cell infiltration, and the reprogramming of tumor-associated macrophages (TAMs). The article also discusses the role of specific signaling elements and inhibitors in targeting WNT/β-catenin signaling, emphasizing the importance of understanding the complex interactions within the tumor microenvironment.The article reviews the regulatory roles of the WNT/β-catenin signaling pathway on the PD-1/PD-L1 axis in the tumor immune ecosystem, discussing its impact on immune checkpoint inhibitor (ICI) therapy responses. Overactive WNT/β-catenin signaling is associated with low immune infiltration, T cell exclusion, and increased regulatory T cells (Tregs) in tumors. It also induces the expression of PD-L1 on tumor cells and promotes PD-1 upregulation, which can lead to resistance to ICI therapy. The review highlights the potential of combining WNT/β-catenin inhibitors with anti-PD-(L)1 agents as a promising regimen to enhance anti-tumor immunity. Key mechanisms include the suppression of Treg cells, increased CD8+ T cell infiltration, and the reprogramming of tumor-associated macrophages (TAMs). The article also discusses the role of specific signaling elements and inhibitors in targeting WNT/β-catenin signaling, emphasizing the importance of understanding the complex interactions within the tumor microenvironment.