The WNT/β-catenin pathway plays a critical role in cancer progression and immune evasion, particularly in the context of immunotherapy. Dysregulation of this pathway is associated with reduced immune infiltration and resistance to immune checkpoint inhibitors (ICIs), such as anti-PD-1 and anti-PD-L1 therapies. The WNT/β-catenin pathway promotes the expression of PD-L1 on tumor cells and enhances the activity of PD-1, contributing to immune evasion. It also facilitates the exclusion of CD8+ T cells and the expansion of regulatory T cells (Tregs), further suppressing anti-tumor immunity. Increased WNT/β-catenin signaling after ICI therapy is linked to resistance, suggesting a potential role in bypassing the effects of these therapies. The pathway is involved in various cellular processes, including epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) expansion, and tumor metastasis. It also influences the tumor microenvironment (TME) by promoting the recruitment of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which further hinder immune responses. The WNT/β-catenin pathway is closely linked to the PD-1/PD-L1 axis, and its activity can be targeted to enhance the efficacy of ICI therapy. Inhibitors of the WNT/β-catenin pathway, such as PORCN inhibitors and Frizzled receptor antagonists, have shown promise in combination with anti-PD-1/PD-L1 therapies. These combinations have demonstrated improved anti-tumor immunity and reduced resistance in preclinical models. The WNT/β-catenin pathway is a promising target for combination therapy with ICIs, particularly in cancers with cold immune profiles and high aggressiveness. However, further research is needed to fully understand the complex interactions between the WNT/β-catenin pathway and immune checkpoint inhibitors, as well as to optimize their use in clinical settings.The WNT/β-catenin pathway plays a critical role in cancer progression and immune evasion, particularly in the context of immunotherapy. Dysregulation of this pathway is associated with reduced immune infiltration and resistance to immune checkpoint inhibitors (ICIs), such as anti-PD-1 and anti-PD-L1 therapies. The WNT/β-catenin pathway promotes the expression of PD-L1 on tumor cells and enhances the activity of PD-1, contributing to immune evasion. It also facilitates the exclusion of CD8+ T cells and the expansion of regulatory T cells (Tregs), further suppressing anti-tumor immunity. Increased WNT/β-catenin signaling after ICI therapy is linked to resistance, suggesting a potential role in bypassing the effects of these therapies. The pathway is involved in various cellular processes, including epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) expansion, and tumor metastasis. It also influences the tumor microenvironment (TME) by promoting the recruitment of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which further hinder immune responses. The WNT/β-catenin pathway is closely linked to the PD-1/PD-L1 axis, and its activity can be targeted to enhance the efficacy of ICI therapy. Inhibitors of the WNT/β-catenin pathway, such as PORCN inhibitors and Frizzled receptor antagonists, have shown promise in combination with anti-PD-1/PD-L1 therapies. These combinations have demonstrated improved anti-tumor immunity and reduced resistance in preclinical models. The WNT/β-catenin pathway is a promising target for combination therapy with ICIs, particularly in cancers with cold immune profiles and high aggressiveness. However, further research is needed to fully understand the complex interactions between the WNT/β-catenin pathway and immune checkpoint inhibitors, as well as to optimize their use in clinical settings.