Tuberculosis (TB) accounts amongst the most deadly infectious diseases worldwide. Despite the availability of a vaccine and effective drugs, Mycobacterium tuberculosis, the etiologic agent of TB, still defies the humanity. An alarming increase in drug resistance and emergence of outbreaks has made it urgent the need for increased surveillance and control. With its structured global geographical distribution, it becomes increasingly clear that this pathogen could have established an advantageous association with its host. Such region-specific host-pathogen equilibrium argues for a TB control at a regional level. The overall objective of the present proposal consists in establishing a network connecting leading institutions in the field from the three North African countries (Morocco, Algeria, and Tunisia) and Europe. The aim is to upgrade the research and surveillance capacity potential of these Europe’s most neighboring Mediterranean partner countries (MPC) through know-how sharing, two-way experience exchange, training, joint research activities, and equipment upgrading. By reinforcing existing human and technological resources in the targeted MPCs, the planned activities will contribute to better address the host and pathogen key factors governing TB transmission/expansion dynamics, emergence of drug resistance, and host susceptibility. This will endow MPCs with higher capacity to better unveil the molecular mechanisms leading to the prevailing epidemiological situation in the specific regional context. Since TB is a health threat common to both sides of the Mediterranean Sea, which is amplified through consistent population migration flows, the planned cooperative initiative could also positively impact on TB control in Europe. Ultimately, dissemination of the project’s results will foster the MPCs’ institutional visibility and scientific competitiveness, allowing them to be more integrated for participation to future European framework program calls.