The main antagonist could be an ancient and malevolent entity that has been sealed away for centuries. Naruto and the Spider Queen's new - found alliance and the combined power they are generating could be what accidentally awakens this entity. It then sets out to destroy both of them and everything they hold dear in their respective worlds.
It could be a powerful dark wizard or sorcerer who wants to control both Naruto's world and the Spider Queen's domain. This antagonist might be after the unique powers that Naruto and the Spider Queen possess, like Naruto's chakra and the Spider Queen's web - based magic. He could try to manipulate them against each other to achieve his goals.
It could be a powerful demon who wants to control the Succubus Queen and use her powers for evil. Since Naruto is with the Queen, he becomes a target too.
It could be the other demons who oppose the Queen of Demons' newfound alliance with Naruto. They might see Naruto as a threat to their way of life or as a tool that the Queen of Demons is misusing. So, they would try to break their bond and destroy Naruto.
Maybe a dark ninja clan that has a grudge against Naruto and also wants to control the Vampire Queen for her powers. They would try to set traps for both Naruto and the Queen, making it difficult for them to trust each other and work together against the real threat.
It could be a powerful dark wizard from the Enchantress' world who follows her to the Naruto universe. He wants to capture the Enchantress and use her powers for his evil plans, and also sees the chakra in Naruto's world as a new source of power to conquer. He could have dark magic that can nullify ninjutsu, creating a real challenge for Naruto and the Enchantress.
Mephisto could also be a great main antagonist. His ability to corrupt and manipulate could pose a real threat to Naruto. Mephisto might try to turn Naruto's friends against him or corrupt Naruto himself. Since Naruto values his comrades highly, this would be a difficult situation for him to deal with. And if Mephisto manages to get into Naruto's head, it could lead to some really intense and dark moments in the fanfiction.
It could be another Predator. Maybe a rogue Predator that doesn't follow the code of its kind. This rogue Predator might see Naruto and his friends as a threat to its own plans in the Naruto world and tries to eliminate them. It could also use its advanced technology against them in cruel ways, making it a formidable antagonist.
It could be a rogue ninja from a long - forgotten clan. This ninja might see the growing relationship between Naruto and Sara as a threat to his own plans for power. He could try to disrupt their villages' alliance and target them specifically.
A new character could be created as the antagonist. Maybe a powerful sorcerer who is jealous of Naruto's presence in Tomoko's world. This sorcerer wants to separate them and take over both worlds. He uses his magic to create illusions that make Tomoko doubt Naruto and vice versa.
It could be an evil ninja from Naruto's world who has somehow discovered a way to travel to Zoe's world and wants to conquer it. He might use his jutsu to overpower the local inhabitants.
Kawaki could also be a potential antagonist. If he feels that Delta's connection with Naruto is a threat to his own place in Konoha or his relationship with Naruto, he might act against them. He has a complex past and his insecurities could drive him to oppose their alliance.