Avian influenza virus (AIV) remains a persistent threat to global poultry production and public health, owing to its ability to infect a wide range of avian and mammalian species. The global resurgence of H5N1 and the limitations associated with control measures in intensive poultry production have highlighted the need for a paradigm shift in disease management strategies. In this context, the development of AIV resilient poultry lines is gaining momentum as a promising strategy for long-term disease management. In this review, we discuss the ongoing threat of AIV to poultry production and explore genetic approaches to enhance resilience against avian influenza. We primarily focus on intracellular host restriction factors that inhibit viral replication, followed by an overview of virus-targeted strategies. We further discuss the use of genome-wide screening approaches to study host–pathogen interactions to identify high confidence host targets. Finally, we highlight studies that develop transgenic, or genome engineered chickens with the aim to enhance AIV resilience and their potential for transforming AIV control in poultry production.