Integrin αV (ITGAV) plays a key role in cell adhesion, migration, and immune regulation, and is implicated in tumor progression. However, its comprehensive expression profile and functional relevance across different cancers remain poorly understood. We conducted an integrative pan-cancer analysis of ITGAV using data from TCGA, GTEx, CCLE, and other public databases. Expression, diagnostic value (via ROC analysis), and prognostic significance (via Cox and Kaplan-Meier analyses of OS, DSS, PFS, and DFS) were assessed. We further explored ITGAV's correlation with immune cell infiltration and immune-related genes, its predictive role in immunotherapy response based on immunophenoscore (IPS), and its drug-binding potential through molecular docking. (1) ITGAV was significantly overexpressed in multiple cancer types including LIHC, COAD, and STAD. (2) ROC analysis confirmed its strong diagnostic value, particularly in HNSC, UCEC, and ESCA. (3) High ITGAV expression was associated with poorer survival outcomes in most cancers, while a protective role was observed in KIRC. (4) ITGAV expression was positively correlated with immune cell infiltration and co-expressed with immune-activating and immunosuppressive genes. (5) The expression level of ITGAV correlates with the IPS score, suggesting its predictive value for the benefit of immunotherapy. (6) Molecular docking identified strong binding affinities between ITGAV and six candidate compounds, including gemcitabine and pioglitazone. Our findings demonstrate that ITGAV is a promising biomarker for diagnosis, prognosis, and immunotherapy prediction across cancers. Its immunological associations and druggability highlight its potential as a candidate therapeutic target.