Our health depends on many factors, some of which are unique to each individual (behavior, genetic factors) and others that are more widely shared within a given population. Thus, addressing environmental risk factors such as air pollution, noise, or heat, and fostering protective and health-promoting factors such as physical activity or nature in the city can help protect and improve the health of the population. These actions also contribute to adapting to climate change, reducing greenhouse gas emissions, and protecting biodiversity, within a systemic vision of health. Quantitative Health Impact Assessment (QHIA) is a formalized method for illustrating the influence of a health determinant on health. QHIA is based on the state-of-the-art scientific knowledge and on local data and scenarios regarding the evolution of the determinants under study. As part of a pilot study, Santé publique France conducted QHIA studies focusing on improving health-promoting determinants (urban green spaces, active mobility) or reducing health-damaging determinants (air pollution, noise, heat) in three French metropolitan areas. This report highlights the main findings for the Lille European Metropolis (MEL). The study covered more than 1.14 million residents. During the study period (2015–2017), an average of nearly 8,300 deaths were recorded each year in the metropolis among people aged 30 and older. The results of these EQIS studies highlight that taking action on green spaces, mobility, air pollution, or transportation noise could prevent several hundred deaths per year in each case (compared to “current” conditions). This represents major health benefits, which would be observed across the entire region, and for some, would be more significant in socially disadvantaged areas. For example, if all the statistical blocks within the MEL had the same level of vegetation as the most vegetated Iris blocks of the same density, 358 deaths would be prevented each year, representing 4.2% of the metropolitan area’s mortality rate; if every resident of the MEL aged 30 and older walked an average of ten additional minutes per weekday, it is estimated that nearly 280 deaths could be prevented each year, representing 3.4% of mortality. An additional ten minutes of cycling per weekday would prevent 475 deaths each year, or 5.7% of mortality; if fine particulate matter (PM2.5) levels everywhere met the value recommended by the World Health Organization (WHO) (5 µg/m³ as an annual average), 965 deaths, or 11.7% of total mortality, would be prevented. This would also prevent nearly 159 new strokes (10.3% of all strokes) and 33 new lung cancers (7.3% of all lung cancers) each year. If nitrogen dioxide (NO₂) levels everywhere complied with the WHO’s recommended limit (10 µg/m³ annual average), 197 deaths—or 2.4% of total mortality—would be prevented. This would also prevent nearly 220 new cases of asthma among children aged 0 to 17, or 7.9% of new asthma cases; if all municipalities in the MEL complied with WHO recommendations for nighttime road noise (45 dB Lnight), this would allow more than 11,600 residents to experience fewer significant sleep disturbances; on average each year, heat during very hot days (average temperature ≥19 °C) was responsible for nearly 92 premature deaths in the MEL. By translating environmental or behavioral data into health impacts, the ÉQIS serve as a valuable decision-making tool to help ensure that health is more systematically integrated into public urban planning policies. The remaining methodological limitations and associated uncertainties do not undermine the significance of the expected benefits of transforming environments to make them more health-promoting.