I recently began rebuilding my bike, stripping it down to just the frame and building it back up piece by piece. One of the decisions I made was choosing the newest Shimano GRX groupset to rebuild with. Unfortunately, I found out the hard way that the new hydraulic brake calipers only work as flat mount only.
It appears that you can take a post compatible caliper and fit it on a flat mount frame with an adapter. However, with flat mount calipers, if you're bike only accepts either post or IS then it would seem you're pretty much shit out of luck.
Now, that's not to say it can't be done. A.S. Solutions offers a few adapters that allow you to fit a flat mount caliper on a post or IS frame. There are limitations though. First, you have to have the clearance on your frame. Second, the IS adapter only works with 180 mm rotors in the front and 160 mm in the back. If these limitations work for you then you're good to go.
For me, I didn't have the clearance nor did I like the idea of having to change my rotors. As such, I ended up taking back the GRX levers and switched them out for some 105 levers that work with mechanical disc brakes. For the brakes, I decided to go with the TRP Spyre brakes. Sucks cause I was really looking forward to a hydraulic brake upgrade. Oh well! Can do that when I upgrade my frame.
In the end, be mindful of the type of brake mounts you have on your frame. If you have anything but flat mounts be prepared to be disappointed if hydraulic brake calipers won't work on your frame.
Update (November 14, 2019)
One commenter made a great point. If you're working with a Shimano groupset, try looking up the groupset in Shimano's latest product compatibility documents. In my case, if I had stuck with a ST-RX810 brake lever then I could have used a BR-RS785 caliper, which is post-mount and can easily be adapted to an IS mount. Pays to do extra research when updating components. :P