A group of rogue ninja scientists could be the antagonists. They've created some sort of technology or experiment that makes it so Naruto can't get help from his friends. They're constantly attacking him with their high - tech weapons and genetically - enhanced ninja beasts while Naruto tries to fight them off on his own.
Maybe an ancient evil ninja who was sealed away long ago but has now been released. This antagonist could have powers that nullify any communication or summoning jutsu, forcing Naruto to fight alone. He would be extremely powerful and know many forgotten and deadly jutsu.
It could be a new dark wizard who is more powerful and cunning than Voldemort. This wizard might have been in hiding all this time, biding his time to take over the wizarding world. With Harry being alone, he would pose a great threat as Harry doesn't have his friends to support him in this fight.
In a 'naruto fights alone fanfiction', it could be that Naruto is on a mission in a foreign land where he has no support. The local ninjas are all against him for some reason. He has to use his Nine - Tails chakra in a more discreet way as he can't afford to go all - out and draw too much attention. He might befriend some local animals or spirits who help him in a more indirect way, like giving him information about the enemies' weaknesses.
A new and powerful Titan could be the antagonist. One that has been hiding in the shadows and now sees Percy alone as an easy target. Maybe this Titan has a special grudge against Percy and wants to take him down while he's vulnerable.
It could be a rogue ninja who created the zombie plague on purpose. Maybe they wanted to take over Konoha or the whole ninja world by using the zombies as an army.
It could be a new and powerful dark ninja who thrives on isolation and wants to keep Naruto alone. He might see Naruto's solitude as a weakness to be exploited.
In this fanfiction scenario, Naruto could potentially use new and untested jutsu. He might draw on the power of his nine - tailed fox in a completely different way. Maybe he'd combine Sage Mode with some secret Uzumaki clan technique he discovers during the fight.
In such a fanfiction, Naruto could potentially win by using his new Sage of Six Paths powers to their fullest. He might be able to overpower Madara's Rinnegan abilities. For example, Naruto could use his massive chakra reserves to create countless shadow clones and overwhelm Madara in a battle of attrition.
Maybe the main antagonist is actually a group of people within Konoha. They might be some of the elders who think Naruto's isolation is a threat to the village's stability. So they send people after him to bring him back, which Naruto sees as an intrusion and they become the antagonists in his eyes.
There's a possibility that the main antagonist is an internal force within Naruto himself. His desire to be alone could be a manifestation of some dark part of his psyche. This 'inner antagonist' could be trying to make Naruto cut himself off from his loved ones completely, leading him down a path of self - destruction. And Naruto has to fight this internal battle while also dealing with any external threats that come his way during his isolation.
Naruto could potentially use a new form of the Nine - Tails Chakra Mode. Maybe he combines it with his Sage Mode in a more seamless way than ever before. This would give him enhanced strength, speed, and the ability to sense danger more acutely.