Another character could be Kakashi. Maybe he has to make a tough decision that goes against Fem Naruto's wishes. For example, not allowing her to go on a dangerous mission she really wants to. This could make Fem Naruto feel betrayed and heartbroken, as Kakashi is a respected figure in her life.
It could also be a new character introduced in the fanfiction. This new character might be in competition with Fem Naruto for something she really wants, like a position in the ninja hierarchy or the affection of another character, and through their actions, they cause Fem Naruto's heartbreak.
It could be a new villain. Maybe a villain who targets Naruto's loved ones and Naruto is unable to save them. This failure would cause him great heartbreak. For instance, if the villain kidnapped Hinata and Naruto couldn't rescue her in time.
It could be Annabeth. Maybe they had a huge fight over something important, like the future of their relationship or a difference in their values regarding their demigod duties. And this fight led to Annabeth leaving Percy, which broke his heart.
Another possibility is that the Pokemon themselves could be the cause, in an unexpected way. For example, if one of Satoshi's Pokemon gets seriously ill and needs to be left in a far - away place for treatment. Satoshi decides to stay with the Pokemon, but Haruka has to continue her journey. This difficult decision could lead to heartbreak for both of 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.
Sakura could be one of her main allies. Sakura, with her medical skills, would be invaluable in taking care of the injured in Fem Naruto's growing empire. Also, Shikamaru, with his intelligence, could help in strategic planning and dealing with political matters.
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.
Sasuke might regret it if he later finds out that Fem Naruto was the key to achieving true peace in their world. Maybe she had a unique ability or knowledge that could have united the warring factions, and by killing her, he doomed their world to more conflict and chaos.
Perhaps it could be a female version of an existing kami from Naruto lore. For instance, a female counterpart of the Sage of Six Paths. She would have vast knowledge and power, and her training of Naruto would be a way to pass on that ancient wisdom and strength.
It could be his arch - enemy. For instance, the Joker might play a cruel trick on Nightwing that makes him lose someone he cares about deeply, thus causing his heartbreak.
C could be an interesting character for Fem Naruto to interact with. C is quite mysterious and has his own set of powers. Their interaction could be full of tension as Fem Naruto tries to figure out what C is really up to. Also, Omoi, with his indecisive nature, could provide some comical relief in Fem Naruto's interactions in Kumo while also being a useful ally in some situations.