For decades, the focus of cultural, social, and economic policies has been shifting to cities. Cities with the highest concentration of creative employment have demonstrated the greatest resilience in the post-2008 economic recovery. Although, over the last few years, there has been an explosion of cultural or creative related indices for cities, no single reference index is commonly accepted. The main thrust of this article is the provision of a systematic and practical framework for a common point of departure for future index developers. To this end, 38 of the most influential culture and creativity indices were reviewed. By adoption of the indicator-driven approach, 16 dimensions corresponding to aspects of culture and creativity were identified in the city context. These dimensions are presented in a novel taxonomy of 3 clusters that aims to distinguish indicators capturing core cultural and creative activities from those oriented on measuring cities' organic background or socio-economic outcomes of the aforementioned activities. In addition, the main obstacles most commonly faced by index developers are described and grouped into 4 distinct conceptual challenges, namely (a) precision, (b) diversity, (c) comparability, and (d) spillover. Each challenge is discussed in detail, accompanied by a systematic approach to its solution.