It could be a rogue ninja who has a vendetta against the Hidden Leaf Village and specifically targets Naruto and Fem Katsuyu because of their unique partnership. This ninja might have some dark jutsu that can counter Fem Katsuyu's abilities.
Another possibility is that an old enemy of the Uzumaki clan resurfaces. They use Itachi's complex relationship with the village and his own motives to manipulate him into kidnapping fem Naruto. So, this old enemy would be the main antagonist as they are the ones driving the overall conflict.
Obviously, the fem Kyuubi herself could be the main antagonist. Since she is the one manipulating Naruto, her actions are causing problems and driving the conflict in the story.
It could be an evil ninja who wants to capture the fem Kyuubi for her power. He might see the unique bond between Naruto and the fem Kyuubi as a threat to his plans of world domination.
It could be an ancient evil spirit that was sealed away by Fem Hashirama in the past. Now that she has resurfaced in the Naruto - era, the spirit is also awakened. This spirit wants to destroy the world that Fem Hashirama once protected and Naruto, being the hero of his time, stands in its way along with Fem Hashirama.
It could be other powerful ninja clans who see the fem Kyuubi's possessive behavior towards Naruto as a threat to their own power and influence. They might try to separate them.
A powerful demon or dark spirit could be the main antagonist. This entity could be attracted to the combined power of Naruto and fem Apollo. It might seek to drain their powers to become even more powerful itself. For example, it could be a demon from Naruto's world that has somehow crossed over into Apollo's realm and is causing chaos there, targeting both Naruto and fem Apollo because they pose a threat to its plans.
It could be another god - like being who is jealous of the female character's powers or her influence in the Naruto universe. This antagonist could be from the same realm as the female character but has different motives. He or she might want to use the chaos in the Naruto world to gain more power for themselves, and the female character stands in their way.
Perhaps a story where Fem Katsuyu and Naruto go on a journey together to find a rare herb that can heal a deadly disease in the village. Along the way, they face various challenges and learn more about each other's strengths and weaknesses. Fem Katsuyu could use her knowledge of the natural world to guide them, and Naruto would use his combat skills to protect them.
It could be an evil wizard from the Fairy Tail world who has somehow gained the power to control demons from the Demon Slayer world. This antagonist would use the demons to cause chaos in both worlds, and the female Naruto character, along with the Demon Slayers and Fairy Tail mages, would have to stop him.
It could be someone from the Naruto universe who doesn't like Naruto's newfound fascination with Aku. For example, Danzo might see Naruto's interest in Aku as a threat to the stability of the village and try to stop Naruto from further exploring Aku - related things. So, Danzo could be the main antagonist in this case.