Air quality plans must be demonstrated to be economically sustainable and environmentally effective. This paper presents a full cost–benefit and environmental analysis of a large regional air quality plan involving several different actions covering a large spectrum of fields, from domestic heating to passenger and freight transport, from electricity generation to agriculture. The impact of each action is analyzed looking at the possible energy savings, greenhouse gases (GHG) emission reductions, the improvement in air quality, and the consequent decrease in external costs, namely the reduced impact on population health. The analysis is performed by applying a flexible and fast computer tool (RIAT+) that allows for a rapid simulation of different pollutant emission scenario, to assess different air quality indices (AQIs) over a regional scale domain. The results show that, in most cases, the economic savings exceed the implementation costs and thus that these actions can be introduced in air quality plans for the domain under study. The reduced health and climate costs, though relevant in absolute terms, are, in general, only a fraction of the economic benefits of energy savings. This is not true for the measures acting on improvements in electricity generation, since a reduction in power plant emissions (generally with high stacks, far from populated areas) does not significantly impact the air quality inside the region. A shift in energy production to renewable sources can instead provide noticeable effects on GHG emissions. This research raises some interesting and general questions about the adequacy of the methodologies applied to attribute costs (and benefits) to actions, improving a variety of sectors that are different from the one in which the measures are applied here.