Shellfish allergy is a significant public health concern, yet the molecular basis of allergenicity in molluscs remains poorly defined. In this study, we performed an in-depth proteomic and immunoinformatic analysis of two widely consumed blood clam species, Anadara broughtonii and Tegillarca granosa, to identify and characterize novel allergen candidates. Using high-resolution tandem mass spectrometry, we generated comprehensive protein profiles and applied three complementary allergen prediction algorithms (SEP-AlgPro™, AllerCatPro,and AlgPred 2.0) to screen for potential IgE-binding proteins. Immunoblotting with sera from shrimp-sensitized individuals confirmed IgE reactivity for nine proteins, including catalase and several hemoglobin isoforms—none of which are currently recognized as molluscan allergens. Homology modeling and sequence alignment revealed conserved structural motifsimplicated in allergenicity and suggested cross-reactivity with known crustacean allergens. These findings expand the repertoire of putative molluscan allergens and demonstrate theutility of integrated proteomic and immunoinformatic strategies for allergen discovery.