A GUID for what? Are you using config ID's or config names to apply configs to nodes? I'm guessing config ID's because the only other GUID would probably be for registration but in either case it would be a no. You shouldn't need to generate a new GUID if you make changes to the config unless you want to apply a slightly different config. Just make your changes, generate a new MOF, create your checksum and throw them both in to the config folder and next time the node that is configured to pull that config polls the pull server it will notice the new checksum and pull and apply the new config.
If you are using ConfigurationNames, you do not need to generate any GUID. Just name your configuration, create a checksum file with the same name. Make sure your target nodes have their metaconfig pointing to this configuration (in the case of an on-prem Pull Server). In case your Pull Server is Azure Automation DSC Service, you can make the assignment between the configuration and the target nodes on the portal UI.