There might be a group of corrupted shinobi who have turned against the Hidden Leaf Village. They view Naruto as a symbol of the village's strength and by getting rid of him, they hope to weaken the village. So Kurama has to constantly be on guard and protect Naruto from their schemes.
Maybe there are powerful dark sorcerers. These sorcerers could be trying to capture Naruto for their own evil purposes, like using his power to open a portal to a dark dimension or something, and Kurama has to protect him from them.
Perhaps there are some shinobi within the village who are jealous of Naruto's potential. They might try to harm Naruto in secret, and Hiruzen has to be vigilant against them. These shinobi could be from clans that have rivalries with the Uzumaki or those who just don't want a new powerful force emerging in the village.
Another possibility is a new and powerful enemy from a neighboring village. This enemy might view fem Naruto as a symbol of the strength of her village and wants to take her out to weaken the village. Shikamaru then has to protect her from this external threat.
It could be Orochimaru. He's always been after power and Naruto's unique abilities would be very appealing to him. So the fem Kyuubi would have to constantly be on guard against Orochimaru's schemes.
In certain 'naruto and kurama team up fanfiction', there are antagonists from other hidden villages. They might be jealous of the power that Naruto and Kurama possess together and want to take it for themselves. So, they plot to kidnap Naruto and force Kurama out of him, which sets off the conflict between them.
The antagonists could be a secret organization within the Hidden Leaf Village itself. They are afraid that if Kurama is freed, it will bring destruction to the village. They think Naruto is being reckless and they will do anything to stop him, including framing him for crimes he didn't commit and turning his friends against him, all in an effort to keep Kurama sealed.
Maybe some of Tony's business rivals who have access to advanced technology. They could be jealous of Tony's relationship with Ultron and try to harm him. They might hire mercenaries or develop their own weapons to go after Tony. In this fanfiction, these rivals would be the main antagonists as they constantly try to break through Ultron's protection of Tony.
In many cases, the main antagonists can be other Slytherins who still hold grudges against Harry or are loyal to the pure - blood supremacist ideology. They might see Harry as a threat to their way of life. Also, some Death Eaters can be antagonists. They target Harry because of his role in Voldemort's downfall and would stop at nothing to get to him.
It could be the Fire Nation remnants who still hold grudges against the airbenders. They might be trying to finish what they started years ago.
Some fanfictions might introduce new original antagonists. These could be powerful rogue ninjas who are after Sakura for her medical skills or some special power she might have in that particular fanfiction. They would then be the main threats that Itachi has to deal with to protect her.
Sasuke could potentially be an antagonist. Even though they were friends before, Sasuke might see Naruto's new fused power as a threat to his own goals or ideals. He could challenge Naruto, thinking that Naruto's power is getting out of hand. Another could be some remnants of the Akatsuki. They might be interested in Naruto's new power and try to either steal it or use it for their own evil purposes.