There are many ways this can go. If Carrie Anne Moss is back it raises a lot of questions regarding the continued nature of the Matrix. Is it basically an immortality machine and there are limited amounts of genepool material for the machines to create humans, so clone. Makes sense, since the Matrix gets rebooted.
The circular nature of the previous matrix worlds can have been broken, so they actually truly live in peace together and the Matrix is now something you plug into voluntarily - perhaps to live out a power fantasy, sorta like a video game. And if they used clones for fuel... then the DNA that made up Trinity may still exist and you can have the existential debate regarding cloning - are the clone the same as the original or its own person, with different wants and desires.
Also... the hive mind of the machines can be explored more. Is it beneficial to the AI that they have one central mind controlling everything or do they crave independence and individuality and the fear and anguish that comes with taking control over your own life.
I didn't like the sequels, but I got what they were trying to say. Humans and machines being dependent on each other, but instead of working together they were exploiting and destroying each other. If we go into this with the humans and machines finally working together... there are no real limits to where the franchise can go... but if they just go back to the same old same old, then it will be dead on arrival, as there's no real reason to go back. Only forward.