I've setup the 3 item webhooks (create, update & delete) so I can sync and log some data on an external service.
They all seem to work as inteded, except for the item.update, which doesn't trigger when a file is uploaded. It triggers when I change another field, but not when only uploading a file and then saving.
I've searched around but haven't found anything on the problem. Is it a setting I'm missing or doesn't the Podio API support this usecase?
In Podio an item and a file are two distinct entities. The behavior you are experiencing is as expected. The item update webhook will only be called when attributes of the item are changed; not when a file is uploaded and associated with an item. If you want to execute a webhook on a file update you'll have to set that up as well.
see 'file.change' hook https://developers.podio.com/doc/hooks