There are several variations of this question in Stackoverflow; repeat the answer, yes, it is definitely possible.
Like most .NET, resource providers are extensible.
I would say that the embedded resource providers (which compile .resx to .resources) are a bad mismatch for web-oriented deployments.
If your settings are mostly strings, you can connect a simple UpdatableResXResourceProvider that uses the built-in ResXResourceReader to read from existing * .resx files.
Results are cached in the application cache.
No assemblies are created - updates are immediately read in the same way as with any other file CacheDependency . At run time, any number of updates can be applied.
The only caveat is that if you do not want to disable the built-in FCNs, you need to move the * .resx files to the shielded folder App_Data strong> (trivially performed with a step after assembly).
You can download UpdatableResXResourceProvider here: http://www.onpreinit.com/2009/06/updatable-aspnet-resx-resource-provider.html
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