Cross-sector, life-course, and setting approaches are identified in the 2015-2018 Regional Prevention Plan (PRP) of Lombardy Region (Northern Italy) as valuable strategies to ensure the efficacy and sustainable prevention of the non-communicable disease (NCDs). The involvement of non-health sectors in health promotion activities represents a suitable strategy to affect on social, economic, and political determinants and to change environmental factors that could cause NCDs. A dialogue among communities, urban planning, and prevention know-how is a prerequisite to develop a system of policies suitable to promote healthy lifestyle in general and, specifically, active lifestyles. The 2015-2018 Lombardy PRP pursues its aims of health promotion and behavioural risk factors for NCDs prevention through programmes that implement their own setting networks (Health Promoting Schools - SPS; Workplace Health Promotion - WHP) and develop new networks. Sedentary lifestyle prevention and active lifestyle promotion are performed through the approach promoted by the Healthy Cities Programme (WHO), encouraging two main processes: 1. creating integrated capacity-building among health and social prevention services, academic research, and local stakeholders on different urban planning and design issues; 2. promoting community empowerment through active citizens participation. Through this process, Lombardy Region aims to orient its services developing evidence-based programmes and enhancing advocacy and mediating capacity skills in order to create a profitable partnership with non-health sectors. This paper reports the main impact data: 26,000 children that reach school by foot thanks to walking buses, 57% of 145 companies joining WHP are involved in promoting physical activity, 18,891 citizens who attend local walking groups.