Zotero allows you to create multiple profiles, each with its own settings and associated data directory. If you're familiar with using multiple profiles in Firefox, Zotero works the same way and supports the same command-line flags.

A default profile is created when you first start Zotero. To create an additional profile, start Zotero from the command line using the same steps as for generating real-time debug output, but replace the -ZoteroDebug flag with -P to open the profile manager.

If you have your Zotero data directory in the default location (“Zotero” within your home directory), the new profile will use that directory by default when you first start it. Create a new directory — e.g., “Zotero Work” in your home directory — and, in the new profile, point Zotero to that one from the Advanced → Files and Folders pane of the preferences.

You can open a specific profile from the command line with the -p flag (e.g., -p Work), which may be useful for creating shortcuts that automatically open a given profile.

Additional configuration may be required when running multiple instances of Zotero at a time.