I want to programmatically (from a plugin) change the \"Other flags\" field in the Miscellaneous settings in the Tool Settings tab for an individual file in a CDT managed build
Generally you can set an option to different objects, i.e. a configuration (if you want the option to apply to all files of a given type in a configuration) or a resource (if you want the option to apply only to the files in a folder or to a single file).
setOption() has multiple prototypes; it looks like you used the one that applies to a file resource.
In my GNU ARM Eclipse Plug-in I successfully used another version:
setOption(IConfiguration config, IHoldsOptions holder, IOption option, String value)
You can see an example in this file, line 583.
I guess this will work in your case too.