One reason could be to seek a new life away from the constraints of Konoha. Maybe they feel that they can't fully grow or explore their potential within the village. Another reason might be to protect Konoha in their own way. They could believe that leaving and dealing with threats from the outside would keep the village safer.
One possible fanfiction could be that Sasuke returns to Konoha after a long mission. Sakura, who has been longing for his return, discovers she is pregnant. This news brings a mix of joy and worry. The village of Konoha is also excited as it means a new generation is coming. Sasuke might initially be shocked but then becomes determined to protect his family and the village.
Sasuke might initially be shocked. He has always seen Sakura as someone connected to Konoha, so her leaving would be unexpected. He could be concerned about her safety, especially if she leaves without proper preparation or protection.
Perhaps in a fanfiction, Sasuke discovers a new and extremely dangerous power that he can't control and it starts to endanger Konoha. Naruto tries to stop him but in the heat of the battle, accidentally kills him. Overwhelmed with guilt and feeling that the village will never understand, Naruto leaves. But this is a very different take on their relationship and the Naruto world as a whole.
Maybe they leave because of a conflict within Konoha. There could be political unrest or a group within the village that they don't agree with. They might think that leaving is the only way to avoid getting involved in something they don't believe in or to protect the village from the inside out in their own way.
Sakura's reaction would depend on how the author writes her character development. If she's become more confident in herself, she might approach Sasuke with a more assertive attitude. She could tell him that she's not the same girl he left behind. However, she'd still have that underlying love for him. She might also be worried about how the village will accept Sasuke's return and how it will affect her standing in Konoha. So her reaction would be a complex blend of personal feelings and concerns for the village.
One reason could be to seek greater power. Maybe they feel that Konoha no longer offers the training or resources they need to reach their full potential. So they decide to leave and explore other places where they can become stronger.
She might leave to find herself. In Konoha, she has always been defined by her relationships with Naruto and Sasuke. Leaving gives her the chance to figure out who she is on her own terms, away from the expectations of her friends and the village.
In the context of Konoha High School, their rivalry could extend to popularity. Sasuke is the cool, brooding type that many students admire from afar. Sakura is popular among the girls for her intelligence and kindness. They both unconsciously compete for the most 'liked' status in school, which creates interesting situations and interactions between them.
Well, it could be about Sasuke coming back to Konoha and Sakura trying to re - establish their relationship. Maybe she's hesitant at first because of all the pain he's caused in the past.