Inherited retinal dystrophies (IRDs) constitute a heterogeneous group of primarily monogenic orphan diseases caused by mutations in over 300 genes, collectively affecting millions of individuals worldwide with visual impairment. Despite significant advances, the development of gene replacement therapy for IRDs has predominantly focused on single-gene approaches, lacking a unified strategy driven by factors such as global prevalence, disease burden, and feasibility of therapeutic delivery. In this review, we propose a comprehensive protocol integrating multifaceted methodologies to refine the identification of suitable gene therapy candidates. We assessed gene prevalence, transcript size compatibility with vector packaging, and cell-type-specific expression, enabling the prioritization of promising therapeutic targets. Our approach focuses on assessing enzyme-coding genes as prime, more suitable candidates for therapeutic intervention due to their relatively similar replacement mechanism. Our findings provide a framework for identifying additional genes that may benefit from similar translational pipelines. This approach revealed a spectrum of potential candidates, including several underexplored genes with high therapeutic potential. Our findings underscore the necessity of adopting a strategic, data-driven framework to prioritize clinically impactful and scalable gene therapy targets, paving the way for broader and more effective therapeutic applications in the field of IRDs. ClinicalTrials.gov identifier: NCT01482195, NCT03316560, NCT06333249, NCT06275620, NCT04850118, NCT05926583.