Pest-control agent, object and symbol of value in past civilisations, companion animal, and iconic celebrity of the web in the modern society, the domestic cat has an intricate bond with humans. This relationship started more than 10,000 years ago, when cats began scavenging and hunting pests that infested granaries of early farming communities in the Near East. Later in history, cats from Egypt dispersed in the Mediterranean following routes of human trade and connectivity. Cats established a unique and intimate bond with humans, and this, together with their adaptability, determined their global dispersal. Yet, the biological and cultural trajectories behind the development of cat-human interactions, and the implications of the global dispersal and evolutionary success of the domestic cat remain enigmatic. By generating a complementary set of unique and as yet unexplored multidisciplinary data, from paleogenetics, to organic chemistry and microscopy, FELIX will dig deeply into the past of the cat-human relationship by tackling three fundamental variables strongly influenced by the domestication process: genomes, food, and microorganisms. It will unravel how the increasing bond with humans across a wide spectrum of socio-cultural contexts, from prehistoric farming communities to the ancient Egyptian and Medieval societies, shaped the cat genome, leading to behavioural changes that turned cats into pets. It will examine how cats changed their nutritional behaviour while adapting to anthropized ecosystems, and document the temporal trajectories of pathogen infections in cats, shedding light on the rise of zoonotic diseases. This will offer unprecedented evolutionary insights on the debate about animal domestication, and will raise public awareness on the role of the cat as cherished pet, but also as one of the world’s most invasive alien species in natural ecosystems and host of infectious diseases recognized today as public health threats.