The study introduces Splicing Neo Antigen Finder (SNAF), a computational workflow designed to identify and prioritize tumor-specific and immunogenic neoantigens derived from splicing events. SNAF employs deep-learning algorithms for immunogenicity prediction and probabilistic models to assess tumor specificity. The workflow is validated using mass spectrometry (MS) and other experimental methods, demonstrating its ability to predict MHC-bound peptides and induce T-cell reactivity. The analysis reveals that splicing neoantigens are frequently shared among patients with melanoma, correlate with overall survival, and can predict response to immunotherapy. Additionally, SNAF identifies a new class of tumor-specific extracellular neo-epitopes termed ExNeoEpitopes, which can be recognized by CAR-T therapies or monoclonal antibodies. The study highlights the potential of splicing neoantigens as shared targets for targeted cancer immunotherapy and provides a comprehensive pipeline for their identification and validation.The study introduces Splicing Neo Antigen Finder (SNAF), a computational workflow designed to identify and prioritize tumor-specific and immunogenic neoantigens derived from splicing events. SNAF employs deep-learning algorithms for immunogenicity prediction and probabilistic models to assess tumor specificity. The workflow is validated using mass spectrometry (MS) and other experimental methods, demonstrating its ability to predict MHC-bound peptides and induce T-cell reactivity. The analysis reveals that splicing neoantigens are frequently shared among patients with melanoma, correlate with overall survival, and can predict response to immunotherapy. Additionally, SNAF identifies a new class of tumor-specific extracellular neo-epitopes termed ExNeoEpitopes, which can be recognized by CAR-T therapies or monoclonal antibodies. The study highlights the potential of splicing neoantigens as shared targets for targeted cancer immunotherapy and provides a comprehensive pipeline for their identification and validation.