First of all, at the end of Fusion, Samus disobeyed the Federation who wanted her to stay put and let them capture the X, but instead she destroyed the B.S.L. and SR388 because she knew the X would absorb them and take over the galaxy if the Federation had their way. Adam and Samus both figured that she would be court martialled for her actions on the B.S.L. and we all assumed Samus would end up an enemy of the Federation, possibly even a fugitive. Yet somehow things are hunky dory enough between Samus and the Federation that they would ask her to go to ZDR in Dread? Now maybe the Federation didn't have much choice because she was the only one immune to the X Parasites, but this was never addressed or mentioned, it's just "LOL welp, business as usual".
Second, there's the issue of Samus being a Metroid. Sakomoto mentioned in an interview once that at the end of Fusion,
when Samus absorbed one of the SA-X, that reset her genetic condition. Yet now in Dread she's still a Metroid? Isn't that a contradiction? I do like the idea of Samus being a Metroid, it opens up a lot for gameplay and storyline purposes and we saw a taste of this in Dread, but this is definitely confusing.
Then later we find out that the X are indeed still alive and locked up in Elun, but Samus accidentally releases them. How did Raven Beak manage to contain them to just this one vault when they spread exponentially like a virus, and why didn't they spread across the universe when released? Releasing the X from Elun seems like it should be game over for the universe, but somehow it's only isolated to ZDR.
Lastly, there's Quiet Robe-X's actions at the end of the game. He suddenly appears in Samus' ship as she's escaping, allowing her to absorb him and revert from her Metroid Suit to escape ZDR. Why did he do this? If Samus is his enemy (which we presume because he's an X and Samus is a Metroid), wouldn't it be better for QR-X to just let Samus die on ZDR where she can't hunt any further Metroids that might still be hiding somewhere in the galaxy? His motivations are somewhat confusing, he's an X but he actually helps her for reasons that don't seem to benefit the X.