Avian influenza remains a persistent global health threat, with Asia at its epicentre due to dense poultry production, live bird markets, and cross-species interfaces with ducks and swine. Several pathogenic subtypes continue to cause recurrent zoonotic spillovers with varying human case fatality, reinforcing the region’s role as a pandemic hotspot. Surveillance highlights the main key ecological drivers: sustained viral circulation in live bird markets, subclinical infection in domestic ducks, wild birds serving as reservoirs, and multiple species with dual receptors that can act as mixing vessels enabling reassortment. Recent events in the United States, where H5N1 has emerged in dairy cattle with viral RNA detectable in retail milk and human cases arising from both poultry and dairy cattle exposures, further demonstrate the capacity of these viruses to invade new mammalian hosts and the food chain. Advances in poultry vaccination and next-generation antivirals show promise but are constrained by antigenic drift, incomplete protection, logistical barriers, and uneven uptake. Human preparedness remains weakened by diagnostic delays, limited access to therapeutics, and fragmented surveillance. Mitigation requires regionally tailored, One Health–driven strategies, market regulation, duck vaccination, swine surveillance, and rapid therapeutic deployment, together with equitable access to tools and transparent international collaboration to reduce zoonotic risk and strengthen global pandemic readiness. This review synthesizes recent evidence on avian influenza virus infections in Asia, outlining zoonotic risks, key drivers, and mitigation strategies, and concludes that the sustained circulation of these viruses in poultry and wild birds continues to present significant challenges for animal health, public health, and pandemic preparedness, highlighting the importance of strengthened One Health surveillance and control measures.