It could be someone who wants to merge their two worlds in a chaotic way. Maybe an evil scientist from Leela's world who has discovered the power of chakra and wants to use it for his own dark purposes. He could try to capture Naruto to study his chakra and use it to take over both universes.
There could be an interdimensional being that feeds on the chaos between different universes. It notices the connection between Naruto's world and Leela's world and tries to create more unrest. This being uses its powers to manipulate people in both worlds, causing mistrust and conflict, and Naruto and Leela have to figure out a way to stop it.
It could be Kaguya Otsutsuki. Since she has powerful abilities and a thirst for power, she would see Kefla's power as a threat and Naruto's influence as something to be eliminated. She might try to manipulate events to turn the ninja world against Kefla and Naruto.
The main antagonist could be an evil merman who wants to take over Ariel's kingdom and is also jealous of her friendship with Naruto. He might use his dark water - based magic to try and stop them.
An ancient evil force that was sealed away by Hashirama long ago could be released in Naruto's time. This entity, having a grudge against Hashirama for imprisoning it, would see Naruto as an obstacle too since he's allied with Hashirama. It could have powers that are completely unknown to the modern ninja world.
It could be Salem herself if the fanfiction focuses on Naruto trying to stop her evil plans. Since Salem has a long history of causing chaos and destruction, Naruto would see her as a force to be reckoned with and try to oppose her.
It could be a rogue ninja from an old clan who has a vendetta against both Konoha and Kumogakure. This ninja has been gathering power in secret and plans to destroy both villages to avenge his clan's past defeat at the hands of the combined forces of the two villages.
Naruto's positive and never - give - up attitude would be a contrast to Leela's more cynical and practical nature. Naruto would be constantly trying to cheer Leela up and get her to see the best in situations. Leela, on the other hand, would keep Naruto grounded and remind him of the practical aspects of their adventures. For example, when they are facing an enemy, Naruto might want to go all - out with his flashy jutsu, but Leela would suggest a more strategic approach using her knowledge of the Futurama world's technology and layout. Their different personalities would create an interesting dynamic as they learn from each other and grow together throughout the fanfiction.
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 character like Orochimaru who somehow gets access to Gotham's technology and becomes even more powerful. He could be creating new types of jutsu using the advanced tech there and causing chaos in both worlds.
It could be a powerful ninja from Naruto's world who has turned evil and wants to use Lara Croft's knowledge of ancient artifacts for his own gain. He might try to force Lara to lead him to the most powerful artifacts so he can become invincible in both worlds.