"Baby Oliver" was cast before he was even born. The producers chose a woman who was pregnant with twin boys who would deliver about the time filming began so the baby would genuinely be a newborn baby, as his character is.
The first gun Smith uses is a Walther PPKS, the usual gun of James Bond. The gun jams on him, and he calls it a "piece of crap." This is an in-joke to the fact that Clive Owen was once considered for the role of James Bond (the role eventually went to Daniel Craig).
When writer/director Michael Davis found his original concept was being continually passed over by the movie studios, he put together a 17 minute reel of animated footage, consisting of 17,000 line drawings with the title card: "This is John Woo's wet dream".
Director Michael Davis and Paul Giamatti had a lot of fun deciding on the look of Giamatti's character, eventually settling on a bad comb over and a slightly lopsided goatee, indicating how sloppy the character could be in some areas. Unfortunately for Giamatti, he made 'Shoot 'Em Up' during the 2005 Oscar season when his film Cinderella Man (2005) was heavily in play, and Giamatti had to attend all the major awards functions looking slightly dishevelled.
In the beginning of the movie, during the rooftop scene, where Clive Owen's character shoots the neon sign to spell out "fuk u", he says "Fuck you, you fucking fucks." That line is taken from the lyrics of the Strapping Young Lad song "You Suck". The band later appears in a music video, on a television.
5 "babies" were used to for the infant in the film. 3 of them were real stunt babies, the other 2 were prosthetic devices. The latter sported guide markings on their face so that the CG artists could map a real baby's face onto the artificial one in the more frenetic action scenes.
There are several references to Warner Bros. animated cartoons throughout the film. Mr. Smith (Clive Owen) is wise cracking and eats carrots like Bugs Bunny, whilst Hertz (Paul Giamatti) hunts him like a darker Elmer Fudd (note the similar facial structure). Also, Hertz's cellphone plays Richard Wagner's "Ride of the Valkyries", which was parodied in the cartoon What's Opera, Doc? (1957) as "Kill the Wabbit".
On the show Mythbusters they tested whether shooting a merry-go-round would cause it to spin like in the film. It proved impossible to spin it with a handgun. Only a much more powerful rifle could cause it to spin, and then only very slowly and with repeated shots rather than quickly with only 1-2 shots as in the film.
This film has several similarities to "Crank" in that 1.) both main protagonists are experts at killing played by British actors who constantly handle guns throughout the separate movies they're in; 2.) both films belong to the action/black comedy genre as well as crime; 3.) almost no explosions whatsoever occur in either movies even though there's nearly non-stop action in both of them; 4.) Jason Statham and Clive Owen both fall from aerial vehicles toward the end of their respective movies (Statham from a helicopter and Owen from a plane); 5.) the directors of both movies also completely self-wrote them; 6.) someone named Michael Davis played a high role in the crew for both films (one of "Crank's" producers and "Shoot 'em Up's" writer/director), even though neither are actually related in real life; 7.) Paul Haslinger composed both films and even has a track titled "Warehouse Shootout" in both soundtracks when the main protagonists get into a gunfight with several enemies at a warehouse; 8.) the separate running times for both films are only two minutes apart from each other ("Crank" at 88 minutes and "Shoot 'em Up" at 86 minutes); and 9.) "Crank" and "Shoot 'em Up" were released nearly one year to the day of each other (the former on Sep. 1, 2006 and the latter on Sep. 7, 2007).
When the villain receives phone calls from his harridan wife, the special ring tone is Richard Wagner's "Ride of the Valkyries". This piece of music was also prominently used in the BMW commercial Star (2001), in which Clive Owen (Mr. Smith) plays The Driver.
Clive Owen was speculated to replace Pierce Brosnan as James Bond in Casino Royale (2006), which Daniel Craig was cast. Monica Bellucci later starred opposite Daniel Craig in the James Bond film Spectre (2015).
Monica Bellucci's character is Donna Quintano, so her initials are "DQ". When she leaves with the baby, Smith tells her not to tell him where she'll get off the bus. He tracks her down to a "Dream Queen," a stand-in for the "Dairy Queen" or "DQ" fast food chain, as well as a play on her character being a specialized lactating prostitute.