Refrigerated raw oysters, including Pacific oysters (Magallana gigas), eastern oysters (Crassostrea virginica), and European flat oysters (Ostrea edulis), are popular seafood products. Pathogenic contamination and spoilage during storage and transport limit their shelf life. High hydrostatic pressure (HHP) and irradiation effectively reduce pathogens and spoilage microorganisms in raw oysters while preserving their taste and texture. This review article presents a comprehensive analysis of the use of HHP and irradiation as sanitation methods for raw oysters, incorporating findings from geographical distribution, mathematical modeling, and radiation quality’s impact on sterilization efficacy. The results demonstrate that untreated eastern oysters can maintain a total bacterial count below the recommended limit of 107 CFU/g for only 2–3 weeks at 5 °C, and are at risk of harboring pathogens such as Vibrio spp. and norovirus. HHP treatment at 600 MPa and irradiation treatment at 2 kGy can effectively reduce the pathogen load in raw oysters. However, supplementary measures such as additional cleaning or lower temperatures are required to prolong the shelf life of treated raw oysters to 2–3 weeks. Taken together, the application of HHP and irradiation to raw oyster sanitation represents a promising approach for enhancing the safety and quality of this beloved seafood delicacy.