Zoonotic spillover is often framed as a property of pathogens: host range, virulence, receptor use, environmental stability, or evolutionary potential. Yet pathogen hazard becomes epidemiologically consequential only when ecological, animal, environmental, behavioral, and host conditions create an interface through which exposure can occur and infection barriers can be crossed. This article develops an original non-empirical One Health architecture that treats the interface, rather than the pathogen alone, as the operational unit of spillover interpretation. The synthesis separates wildlife reservoir context, livestock and companion-animal interfaces, human behavior, food and water pathways, environmental persistence, contact intensity, contact-network structure, host susceptibility, and pathogen compatibility, then considers how these dimensions can combine to amplify or constrain risk. The proposed architecture does not assign a universal score or assume that detected pathogen, environmental persistence, molecular adaptation, or animal infection is equivalent to human transmission. Instead, it organizes heterogeneous signals around interface states, evidence boundaries, and reassessment needs. Contemporary highly pathogenic avian influenza A(H5N1) in dairy cattle provides a high-resolution example, while broader viral, bacterial, ecological, and network evidence prevents the model from becoming outbreak-specific. The architecture is intended to support surveillance design, intervention targeting, and cross-sector interpretation before and during emergence. Its propositions remain context-dependent and require prospective, multispecies, route-specific, and externally replicated validation before predictive or operational performance can be claimed. Risk is consequently treated as dynamic and revisable as interfaces change through movement, husbandry, behavior, environmental conditions, surveillance findings, or intervention.
