This study focuses on the space-time patterns of the COVID-19 Omicron wave at a regional scale, using municipal data. We analyze the Basque Country and Cantabria, two adjacent regions in the north of Spain, which between them numbered 491,816 confirmed cases in their 358 municipalities from 15th November 2021 to 31st March 2022. The study seeks to determine the role of functional urban areas (FUAs) in the spread of the Omicron variant of the virus, using ESRI Technology (ArcGIS Pro) and applying intelligence location methods such as 3D-bins and emerging hot spots. Those methods help identify trends and types of problem area, such as hot spots, at municipal level. The results demonstrate that FUAs do not contain an over-concentration of COVID-19 cases, as their location coefficient is under 1.0 in relation to population. Nevertheless, FUAs do have an important role as drivers of spread in the upward curve of the Omicron wave. Significant hot spot patterns are found in 85.0% of FUA area, where 98.9% of FUA cases occur. The distribution of cases shows a spatially stationary linear correlation linked to demographically progressive areas (densely populated, young profile, and with more children per woman) which are well connected by highways and railroads. Based on this research, the proposed GIS methodology can be adapted to other case studies. Considering geo-prevention and WHO Health in All Policies approaches, the research findings reveal spatial patterns that can help policymakers in tackling the pandemic in future waves as society learns to live with the virus.