It could be that there is some misunderstanding between them. Say, Misty misinterprets something Ash does as him not caring about her anymore. Ash, being clueless about her misinterpretation, doesn't correct it in time. Then Misty distances herself from him, and Ash is left heartbroken when he finally realizes what has happened.
It could slow him down. Ash might be so distraught that he doesn't focus well on training his Pokemon. His usual enthusiasm for battles and catching new Pokemon might wane, as his mind is preoccupied with his broken heart.
One possible reason could be unrequited love. Maybe Natsu has feelings for someone who doesn't feel the same way about him. This could lead to his heartbreak as he realizes that his love is not reciprocated.
A new, powerful villain could be the cause. This villain might target Ash's Pokémon and manage to steal them all away. Ash would be heartbroken not only because he lost his Pokémon but also because he feels he has failed to protect them.
Well, it could be due to the failure to protect the village. Naruto has always been about protecting Konoha. If something really bad happened, like a major attack that he couldn't prevent and many lives were lost, he might feel so much guilt and heartbreak that he decides to leave. He would feel like he failed his purpose.
Well, perhaps in the fanfiction, Ash is betrayed by a group of friends he trusted deeply. They might have used him to get access to some rare Pokémon or some important information, and then they turn their backs on him. This would be a huge heartbreak for Ash, who is always so loyal to his friends. Or it could be that he fails to achieve a major goal like winning a big Pokémon tournament due to some unfair circumstances, and he feels heartbroken as all his efforts seem to be in vain.
Gary could also be the one to cause Ash's heartbreak. Maybe Gary outshines Ash in a big Pokemon battle and then mocks him for it. This could make Ash feel like a failure and break his heart. Gary has always been a bit of a rival to Ash, so this kind of situation is plausible in fanfiction.
One possible reason is a difference in goals. Ash might be focused on one type of Pokémon journey, like competing in a particular league. Misty, on the other hand, could have a different long - term goal, like protecting a specific water - type Pokémon habitat. If their goals start to conflict, it could lead to a situation where Misty seems to betray Ash to further her own aims.
One reason could be that both Ash and Gary have only just realized their feelings for Misty at the party. They might have been suppressing their emotions before. Ash could see Misty in a new light, perhaps because of how she looks or behaves at the party. Gary, too, might suddenly feel a strong attraction and not want to lose her to Ash.
In some fanfics, Misty might be portrayed as betraying Ash for power. For example, if there is a powerful trainer who offers Misty a chance to become an even greater trainer, but at the cost of leaving Ash behind. She could be tempted by the allure of advanced training techniques or rare Pokémon that this new opportunity presents.
One common theme is unrequited love. Maybe Ash has feelings for a character who doesn't feel the same way back. Another could be betrayal. For example, a friend or a loved one betrays Ash, which leads to his heartbreak. Also, the theme of loss can be present, like losing a Pokemon that was very close to him, which shatters his heart in the fanfiction.