The comic teamed up with the basketball superstar for the 2015 film, which marked LeBron's movie debut, and now both are starting to talk about a follow-up.
Reposting a fan's note on Instagram, which read, "We need another film with both of you together. Trainwreck is too darn funny," Amy asked James, "Is this time next year good for you?"
He replied, "I think we can make that happen! Trainwreck 2???" along with a shrugging emoji.
Thrilled Schumer then gave fans of the film a big boost, writing, "Legoooooooo (sic)."
In the film, Amy played an unlucky in love magazine writer, who falls for Bill Hader's sports doctor. His best friend is played by LeBron.
Actors Frawley and Vance played neighbours Fred and Ethel Mertz in "I Love Lucy".
The movie will follow the couple and their associates over the course of a week, as Lucy and Desi face a crisis that could end their careers and another that could end their marriage, according to Deadline.
Lucie Arnaz and Desi Arnaz Jr., Lucille and Desi's kids, are among the film's producers.