Smoking is the largest avoidable cause of preventable morbidity worldwide. It causes most of the cases of lung cancer and chronic obstructive pulmonary disease (COPD) and contributes to the development of other lung diseases. SmokeFreeBrain aims to address the effectiveness of a multi-level variety of interventions aiming at smoking cessation in high risk target groups within High Middle Income Countries (HMIC) such as unemployed young adults, COPD and asthma patients, and within the general population in Low-Middle Income Countries (LMIC). The project addresses existing approaches aimed to prevent lung diseases caused by tobacco while developing new treatments and evaluating: (i) Public Service Announcement (PSA) against smoking, (ii) the use of electronic cigarettes, (iii) neurofeedback protocols against smoking addiction, (iv) a specifically developed intervention protocol based on behavioral therapy, social media/mobile apps and short text messages (sms) and (v) pharmacologic interventions. Emphasis in this paper, however, is placed on the e-heath, m-health, open (big) data, mobile game and neuroscientific challenges and developments upon facilitating the aforementioned interventions.