During the last two decades, the labour market of the advanced economies has changed, with the increased use of short-term contracts and higher flexibility in terms of working spaces and work organization. Due to ongoing processes of the globalization and the Industry 4.0 Revolution, distance, location, and time are often no longer considered necessary conditions to make business. In this context, we have witnessed the development and diffusion of coworking spaces (hereinafter CSs). This chapter aims to investigate and compare development, typology, and dynamics of spatial distribution of CSs in two alpha global cities, Prague and Milan, between 2015 and 2019. Using two original geo-referenced databases, the chapter firstly proposes two metrics for quantitative mapping of CSs within basic settlement units in Prague and local identity units in Milan. Local spatial autocorrelation is used to identify spatial clusters in given years, and local spatio-temporal analysis investigated by differential spatial autocorrelation is applied to identify whether changes in spatial patterns over time are spatially clustered. Based on these findings, the chapter highlights similarities and differences in spatial patterns, spatial diffusion, and evolution of CSs in the two cities. Secondly, the chapter provides a discussion on micro-location of CSs in relation to the internal urban spatial structure and its transformation (urban core commercialization, inner city urban regeneration, and gentrification) and thereby the transition to the polycentric city model.