Speaking during a panel discussion at the Tribeca Film Festival on Thursday (April 19), De Niro explained that the follow-up to the 1988 action comedy would focus on his character helping the son of the criminal accountant from the first film.
The actor said of his character Jack Walsh: "He got himself in trouble. So that's where we are. The script is being reworked. I hope to do it - it was a lot of fun to do."
It was reported last month that director Brett Ratner is in negotiations to direct the sequel.
De Niro, who founded the Tribeca Film Festival in 2002, is currently in talks to join the cast of the upcoming CBS show Last Vegas.
The panel, mediated by director Judd Apatow, was in honour of the 100th anniversary of Universal Studios.
Apatow and De Niro talked about several of the veteran actor's Universal movies including Mean Streets, King of Comedy and Raging Bull, which De Niro said he would return to if the "script was good".
Watch the trailer for Midnight Run below: