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Demand for seafood products is increasing worldwide, contributing to ever more complex supply chains and posing challenges to trace their origin and guarantee legal, well-managed, sustainable sources from confirmed locations. While DNA-based methods have proven to be reliable in verifying seafood authenticity at the species level, the verification of geographic origin remains inherently more complex. Both genetic and stable isotope analyses have been employed for determining point-of-origin with varying degrees of success, highlighting that their application can be effective when the right tool is selected for a given application. Developing an a priori prediction of their discrimination power for different applications can help avoid the financial cost of developing inappropriate reference datasets. Here, we reviewed the application of both techniques to seafood point-of-origin for 63 commercial finfish species certified by the Marine Stewardship Council, and showed that, even for those species where baseline data exist, real applications are scarce. To fill these gaps, we synthesised current knowledge on biological and biogeochemical mechanisms that underpin spatial variations in genetic and isotopic signatures. We describe which species' biological and distribution traits are most helpful in predicting effectiveness of each tool. Building on this, we applied a mechanistic approach to predicting the potential for successful validation of origin to three case study fisheries, using combined genetic and isotopic methodologies to distinguish individuals from certified versus non-certified regions. Beyond ecolabelling applications, the framework we describe could be reproduced by governments and industries to select the most cost-effective techniques.