GIS: At its simplest, a geographic information system (GIS) creates maps and connects them to databases. QGIS is a good open-source, free alternative.
ArcGIS CityEngine: An expensive but powerful solution for the creation of massive urban environments. It is very good at incorporating actual locations, and allows for the importing of real geographic & topographic date.
CAD: Computer Aided Design (CAD) software is the standard tool of the engineering and architecture industry. AutoCAD is the most famous CAD, but quality free solutions like LibreCAD can handle most of a game city’s needs.
Campaign Cartographer: Mainly designed to create maps and cities for tabletop RPGs, the Campaign Cartographer can be expanded with the City Designer that allows for the design (and illustration) of fantasy cities.
Inkarnate: Allows for the creation of fantasy maps.
Gaia: An impressive, professional tool for semi-procedurally generating digital geographies (to spec).
Houdini: A procedural tool built for modularity and perfectly capable of helping with the generation of large urban settings.
OSM Importer: Allows you to import data from the Open Street Maps database into Houdini.
Miro: An excellent collaborative tool for gathering references (and more), that I find crucial to the design of game cities.
Streetmix: Wonderful tool for designing contemporary streets with bike paths, sidewalks, etc.