Uncontrolled urban growth in South Mediterranean and the Middle East regions involves city dwellers and stray animals (mainly dogs and cats) creating a dense and downgraded environment, in which irregular street garbage collection disposes sufficient food for survival and proliferation of stray animals. Under such conditions serious public health hazards are expected due to the increase of animal bites, the multiplication of insects and rodents vectors of different viral, bacterial, fungal and parasitic agents to which humans are exposed. Traditional national stray animal eradication programs and occasional small animals' humane elimination campaigns are insufficient to avert human and veterinary health risks when not coupled with modern technologies. In such environments, multiple foci of emerging and re-emerging zoonoses easily spread, i.e. rabies, hydatidosis, leishmaniasis and toxoplasmosis. Upgrading urban and peri-urban situations requires integrated/coordinated management programmes, in which public and animal health services as well as municipalities have a crucial role. Control and upgrading programmes should be flexible and able to adapt to the specific conditions of the given country/region. In this context, intersectoral/interprofessional collaborations and community participation are crucial for any national and regional development strategies. In this respect, a global approach considering both public health and socio-economic problems shows to be extremely adequate and effective.