Is it likely? He was in all three of the previous Spider-Man movies in some form or another...
Would Willem DaFoe be willing to do a 4th appearance in the popular Spider-Man movie franchise? iF MAGAZINE interviewed the actor and posed the question.
DAFOE: [Laughs] I had to think back to what I did on all three. It would depend on a lot of things not just on schedules that stuff can get worked out. It would depend on who is involved and what they want me to do. I feel like I was slowly exiting. The first one was fun to do, the second one there wasn’t much to do, but I did it because I like Sam [Raimi], and then in the third one I was a shadow. I can’t imagine unless there was something to do like a resurrection that they did in the comic book that would be fun to do. Never say never though!