There is a slew of villains that Deadpool could bring in for his next outing, which is rumored to include Wolverine as well. However, there are few villains that could actually do any lasting damage to the Merc with a Mouth.
Deadpool could get one of the other generic X-Men villains to be a part of his film, or he could introduce a terrifying villain into the MCU who would not only be a threat to him but also to the likes of Wolverine.
Deadpool 4 should introduce Death Grip into the MCU
Death Grip is a character who has the ability to absorb life forces and souls, which is how he managed to absorb the abilities of the Muramasa Blade, which famously nullifies any sort of healing factor that heroes like Deadpool and Wolverine have.
Deadpool 4 could introduce the character into the Marvel Cinematic Universe, posing a threat to everyone from Deadpool to Wolverine, and other mutants who have a healing factor as well. Given that magic exists in the MCU in earnest, there will not be an issue for Deadpool to face off against a magic-wielding villain.
Perhaps the film could have the likes of Doctor Strange, Iron Fist, and Moon Knight assisting Wolverine and Deadpool. This could have Deadpool interact with other parts of the Marvel Cinematic Universe, which could create the sense of cohesion that the universe has been missing for so long.
Death Grip could actually be introduced in a Wolverine film instead
Wolverine in the Marvel Cinematic Universe will be played by Hugh Jackman for some time to come. This means that Wolverine could get another solo film, which could also introduce a character like Death Grip. The Muramasa blade made its appearance in the comics as an instrument against Wolverine, one of his own sons, Daken, melded into his claws to fight his father.
This could result in a story where Death Grip and Daken are melded into the same character, as a unique villain for Wolverine to face off. The Wolverine that audiences saw in Deadpool & Wolverine still had some unresolved guilt, which could come in the form of him getting a second chance to be there for those he loves (his children) and messing it up once again.
