Highly pathogenic avian influenza (HPAI), with a current focus on the emergent H5N1 clade 2.3.4.4b, remains a substantial and evolving threat to animal health, food security, and zoonotic safety. Since early 2024, novel genotypic variants within this clade have driven widespread epizootics across US poultry and dairy production systems, along with zoonotic transmission events. With the depopulation of over 168 million birds and economic losses exceeding 1.4 billion USD since 2022, recent outbreaks highlight the urgent need for complementary, decentralized, real-time biosurveillance strategies. This review outlines the molecular pathobiology and transmission kinetics of contemporary HPAI strains and evaluates diagnostic bottlenecks. Then, we explore how molecular amplification, electrochemical detection, and acoustic anomaly analysis can be combined into a single approach for in situ disease recognition. Finally, we describe how behavioral and physiological signal integration can enhance biosensor accuracy and support adaptive One Health biosurveillance systems for anticipatory and scalable field responses.