Multiple File and Single File/many tables both work. Both are supported by Filemaker.
Single File solutions:
1) Aren't likely to break if someone moves or renames a file.
2) Have fewer issues managing relationships between tables.
3) Enable you to see all the relationships between all the tables in one window.
4) You'll only need to manage one set of accounts/passwords/access priviledge settings.
5) Aren't like to hit the "50-80 open file" limit.
6) Scripts must carefully take into account which layout/table is "current" during execution.
Multi File solutions:
1) Can enable a developer to mix and match components to produce different solutions.
2) Can avoid "visual clutter" because they don't show every relationship in one window.
3) Each file has it's own set of Accounts/passwords/access priviledge settings. --- This is usually a big problem, but may be helpful in some situations.
Others may have different observations, but those are what I come up with.