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.
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.
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.
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 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.
In Kalos, one potential rival for Ash could be a local trainer who specializes in Fairy - type Pokémon. Fairy - type Pokémon can be quite tricky in battles, and this trainer has mastered the use of their unique abilities. For Misty, a rival could be a girl who is an expert in water - type Pokémon battles, just like Misty herself. This girl might have some rare water - type Pokémon from Kalos that Misty has never seen before.
In Ash and Misty relationship fanfiction, their relationship is often portrayed as a deep and evolving one. They start as friends on their Pokémon journey. Ash's determination and Misty's feisty nature create a great dynamic. They support each other in battles and through various challenges, and over time, a romantic undertone may develop as they grow closer and understand each other better.
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.
Fanfiction about Ash and Misty's romance can take many forms. It could be set in different regions they've visited in the Pokémon world. Maybe in a story, they get separated during a journey and the longing they feel for each other during that time becomes the catalyst for their romantic feelings to surface. Some fanfic authors also like to include other Pokémon characters to add more drama and humor to their relationship.