Another scenario could be that they are poisoned by a new, undetectable toxin. As they gradually weaken, they try to find a cure but run out of time. Their deaths would be a great loss, and it could lead to major changes in the political and social structure of the ninja world as everyone copes with their passing.
Another scenario could be that Naruto and Sasuke discover a new power within themselves during the fight against Kaguya. This new power could be related to their friendship or their connection to the Sage of Six Paths. They then use this power to finally defeat Kaguya.
Well, in some versions of this fanfiction, it might be that Naruto uses a powerful and forbidden jutsu to defeat an overwhelming foe. This jutsu drains his life force, and Sasuke, who has just realized how much Naruto means to him, catches Naruto as he collapses. It could also be that Naruto is poisoned, and Sasuke tries his best to save him but fails in the end, and Naruto passes away in his arms.
Perhaps Naruto has some sort of premonition about Sasuke's danger. He follows his gut feeling and finds Sasuke trapped by Haku. He then uses his Uzumaki bloodline power, something that might be enhanced in fanfiction, to disrupt Haku's chakra flow and save Sasuke.
Maybe in a moment of reconciliation. After years of being apart and having misunderstandings, when they finally come back together and forgive each other, the emotions are so strong that a kiss just happens. It could be a very emotional and slow - building moment, with lots of words of apology and understanding first.
One possible scenario is that Naruto loses all his powers. He has been defined by his strength and his ability to protect. Without it, he may feel useless and worthless, leading to a desire to die. For instance, if he is cursed and loses his chakra completely.
Well, perhaps in a fanfiction, Sasuke could cry for Sakura when he discovers a deep secret she has been hiding. Maybe it's something that makes him understand her on a whole new level, like a hidden pain she has endured all this time for his sake. This newfound understanding could stir such strong emotions in him that he can't hold back his tears.
One possible scenario could be they sacrifice themselves to save their friends. Maybe they are facing an all - powerful enemy that can only be defeated if they give up their own lives. For example, if there is a dark force threatening to destroy their entire world and the only way to stop it is by using their combined powers in a self - destructive way.
Maybe Naruto's illness is a result of some dark jutsu used against him. His illness could lead to him being unable to perform his ninja duties, and so his friends, like Sasuke and Sakura, have to take on extra missions to protect the village while also trying to find a way to heal him. They could search through ancient ninja scrolls for a remedy.
One interesting scenario could be that Naruto and Sasuke discover a new power within themselves during the fight that changes the whole dynamic. Maybe Naruto unlocks a new form of Sage Mode that gives him an edge, and Sasuke responds with a new sharingan evolution.
Maybe Itachi gets sick. Then Sasuke has to take care of him, getting medicine and staying by his bedside. He'd worry about Itachi's health and do everything he can to make him better.