You know the Karma Seal can only be given when the Otsutsuki is almost killed,like how Isshiki gave Karma to Jigen and how Momoshiki gave Karma to Boruto.That’s the natural way of giving Karma.
But Kawaki got it through a different process.He got his Karma artificially.That is Isshiki with the help of Amado just transfered a part of his Karma on Jigen to Karma. Now that Isshiki has been revived,he can’t give Karma artificially.
If that is the case then now Isshiki has been revived in Jigen’s body.And since Jigen is a defective vessel , Isshiki revived defectively or isn’t at fullpower either.Or else why would he place Karma on Kawaki ?
So with help of available information Isshiki has to be nearly killed so that he can place Karma on Kawaki.But Isshiki inside Jigen,a defective vessel,almost killed Naruto and Sasuke. Now that he is revived he should be atleast more powerful than while he was inside Jigen. So this Isshiki could easily kill Naruto and Sasuke.They satnd no chance.
And how can he be defeated ?
Isshiki from what I have seen has no intention of giving up Konoha.All he wants is Kawaki . So I think Isshiki will say “Give me Kawaki or I destroy Konoha”.Though Naruto is reluctant he is forced to give Kawaki away by the others.Kawaki’ who almost accepted Naruto as his father figure , is deeply hurt.And that is what causes him to say what we saw in the first episode.
In my opinion what will happen is that Naruto and Sasuke have almost learned of all abilities of Isshiki coupled with Amado’s info about how to kill an Otsutsuki,they should take him down, paving way for Isshiki to naturally place Karma on Kawaki.
This is just a theory/assumption,may be there is third way of placing Karma or maybe it is the Karma of an entirely new unknown Otsutsuki, so don’t take it seriously.