This study highlights the need and suggests some basis for working on the Life Cycle Assessment (LCA) of cities with a sustainability perspective. Cities are relevant actors in sustainable development and contribute to the generation of significant environmental impacts upstream and downstream their internal activity. LCA is precise in assessing environmental aspects of sustainability but lacks social and economic inputs. It is important to avoid problem shifting, even between the different dimensions of sustainability. A systematic literature review has been performed so as to extract the procedure for defining the goal, function, functional unit, and reference flow of a complex system. The existing literature is mainly product focused, although services are also considered somehow. The procedure for defining the abovementioned items is previously applied to a relatively simple system, a power generation plant, so as to find parallelisms to define those items for a complex system such as a city. To obtain a feasible (i.e., simplified) city Life Cycle Sustainability Assessment, the authors propose to introduce the social and economic aspects through the use of the City Prosperity Index (CPI) as technical performance within the FU of the city LCA. The CPI combined with the number of inhabitants is the normalization factor which is found to be more suitable to avoid problem shifting among sustainability dimensions and to avoid the interference of the number of inhabitants when comparing two different cities. An exemplification of the variation of the results after the application of these two factors in 18 cities’ CO2-eq emissions is described. Even though this is not a large sample, it includes cities from different continents and levels of development and, thus it can be useful to see the how the suggested method is affecting cities’ ranking.