The British actor spent the best part of a decade playing devious Lucius Malfoy in the Potter films and he tells WENN he'd love a shot at following Javier Bardem, who plays Skyfall's evil mastermind Raoul Silva.
He says, "I'd love to be a Bond villain. I've never been approached and I've never been available... I was signed up to Harry Potter for years and other things but I would do it in a heartbeat, particularly because I'm a big fan of Daniel Craig's; I think he's a terrific Bond."
And Isaacs insists such casting would make for an interesting side story: "Dan and I played lovers for a year onstage at the National Theatre in London in Angels in America, so it might be the perfect bookend for our screen relationship.
"That was possibly the artistic highlight of my life; I don't know if he would say the same thing."
It appears Craig does have some weight with the Bond bosses - he suggested they hire Sam Mendes as director for Skyfall after an exchange with the fellow Brit at a party.
But Isaacs doesn't appear to be the favourite to play a Bond villain among film fans - Gary Oldman topped a recent Fandango poll to find the actor 007 devotees would most like to see up against the superspy.
He beat out Oscar winners Daniel Day-Lewis and Christoph Waltz, Viggo Mortensen and Charlize Theron.
Kevin Spacey, who also recently expressed a desire to portray a Bond baddie, also made the top 10 alongside Russell Crowe, Steve Buscemi, Tilda Swinton and Daniel Craig's real-life wife Rachel Weisz.
Meanwhile, in a related poll, Gert Frobe's Goldfinger has topped a new list of the best Bond villains.
The German star's devious mastermind beat out Donald Pleasance's Blofeld from You Only Live Twice and Richard Kiel's metal-toothed monster Jaws from Moonraker and The Spy Who Loved Me.
Christopher Walken's Max Zorin and Christopher Lee's Scaramanga also made the top five.