Rapid advancements in genomic medicine, particularly in viral vector-based delivery systems, underscore the necessity for AAV capsids suitable for translation from rodent models to humans. Therefore, there is a high need for a robust platform to assess the tropism and potency of engineered capsids. In our study, we focused on liver-tropic capsids and conducted a comprehensive analysis across diverse models, including ex-vivo primary human hepatocytes, in vivo wild-type (WT) mice, different liver humanized mouse models (FRG mouse versus PXB-mouse), and non-human primates (NHP), to evaluate the transduction efficiency of different liver-specific capsids designed for genomic medicine applications. In primary human hepatocytes, WT mice, and humanized mouse models, we employed reporter genes GFP and human FIX to evaluate transduction efficiency in different models. Droplet digital PCR measured GFP RNA expression levels, GFP protein was quantified by IHC staining, and ELISA was used to measure human FIX protein levels. In the NHP study, we barcoded different capsids and validated transgene RNA levels quantified by next-generation sequencing (NGS). Consistent results were observed for capsid ranking in two different liver humanized mouse models, FRG (FAH KO) and PXB-mice (cDNA uPA/SCID), aligning with the outcomes in human primary hepatocytes. The FRG mouse had roughly 50% human hepatocyte engraftment, while the PXB-mouse had 90% human hepatocyte engraftment. Notably, the top capsid from human models also demonstrated excellent transduction efficiency in the WT mouse liver, suggesting its potential use in preclinical, primate, and human studies. Importantly, the lead capsid identified in the WT mouse study, humanized mice, and primary human hepatocytes remained the top performer in the NHP study, the most relevant model to humans for liver-tropic capsids. The results of this comparative analysis not only deepen our understanding of capsid behavior but also lay the groundwork for a standardized screening platform for capsids, streamlining preclinical testing across diverse species. The identification of a common capsid with tropism and transduction capabilities across various species represents a significant advance in the field of genomic medicine.