ITA Matrix has had issues with married segment inventory when pricing itins hop-by-hop using multi-city for many years. It's definitely not a new thing. If you use one-way or roundtrip searches and use it's advanced controls features to specify routings, it should be fine. The problem with using multi-city hop-by-hop is that it only checks invididual flight class inventory availability when specifying a fare quote covering multiple segments. It doesn't actually check married segment inventory availabilty which is required when combining the multiple segments on one fare. If multi-city connections are over 24 hours (on most international itins), it can't combine segments on a single fare as it creates a stopover and should also be okay as married segment inventory is no longer involved.

Google Flights has had similar issues over the years (Google bought ITA and the underlying technology likely comes from them). I believe it still has issues with some airlines, although it has come up with a "fix" with Delta flights. If you are using multi-city to specify an itin hop-by-hop with Delta flights, Google Flights will do a final married segment inventory check on flights after the last segment has been selected and update the fare quote if married segment inventory does not match individual flight segment inventory.

Here's an example of a Google Flights multi-city search for Delta flights where it's corrects a fare quote due to no married segment availability. It's initially quoting a $248 X basis fare on flights. But then changes it to a $289 U basis fare after the final segment is selected as there is only married segment inventory availability for the combined flights in U class as seen on ExpertFlyer. Individually, the flights both have X inventory availability, but you have to use married segment inventory availability when combining the two flights on one fare. Note that for US48 domestic connections, DL/UA/AA all have a maximum connection time of 4 hours on flights in order to book them on one fare. Once you are over that, a stopover is created and their fares do not allow stopovers on US48 fares. This means each segment will be booked on a separate fare in those cases and married segment inventory availability is no longer an issue.