In the level Castle's Apartment, the game's principal artist Frank Marquart hid references to rock musician characters from other Marvel properties on posters throughout the room, as part of an effort to include references to the larger Marvel universe in the game:

• After the Punisher smashes the Russian's head into a few computer monitors and retaliates by tossing Punisher through a wall into a bathroom, a poster with the words "Lila" and a guitar can be seen. This is a reference to the X-Men character Lila Cheney, an intergalactic teleporting mutant who is a famous rock star within the Marvel universe.
• Another poster can be seen near where the Punisher lands after the Russian throws him through a wall into the computer room. The poster has eyes and a unique marking, with the text "Dazzler" above them. This is a reference to the X-Men character Dazzler, a mutant with the ability to convert sound vibrations into laser beams, and much like Lila Chaney, is a popular pop star in the Marvel universe. The poster incorporates Dazzler's blue 1970s-inspired make-up.
• On a wall to the left of the monitors, a poster with the text "Steal This Planet! A Rock Fable" can be seen. This is a reference to New Mutants Annual (1984) Issue #1, and features the first appearance of X-Men character Lila Cheney in a plot to steal the earth.

Considering that a major gameplay mechanic was torturing criminals with precise control over the intensity of the torture and their suffering, Volition knew that The Punisher could cause problems with the Entertainment Software Ratings Board. The game had to be submitted to the ESRB multiple times over the course of three weeks to avoid the Adults Only rating, which would have prevented the game from being sold at major retailers. Volition submitted the game earlier than usual to get an idea of what was and wasn't allowed so they could achieve a Mature rating. Examples included removing certain executions, positioning the camera so the player wouldn't see certain actions, deducting points if the player kills criminals after successfully or unsuccessfully gaining information during an interrogation, and adding a black-and-white filter inspired by the 2004 film "Kill Bill" over the more extreme deaths. After the game released, the ESRB actually used Volition as a positive benchmark for how to coordinate and communicate with them.

During the level Stark Towers, after killing one of the Yakuza grunts, another one of them will say upon discovering his body: "Oh no! They've killed Kenji!" This is a reference to a running gag from the adult animated series "South Park", where one of the four main characters Kenny frequently gets killed towards the end of the episode, causing his friend Stan to yell: "Oh my God! They killed Kenny!"

Much of the game's dialogue, characters, plot and even comic panels (through The Punisher's Flashbacks) are lifted from the comic book arcs "The Punisher: Welcome Back, Frank" and "The Punisher MAX". One of the game's writers Garth Ennis also wrote for both comics, while another co-writer Jimmy Palmiotti inked artwork for "The Punisher MAX".

The game was originally pitched as being in a first-person perspective, but was soon changed to third-person so that players could see the Punisher as he was fighting.

Some Marvel cameos and references had to be removed during development, as Volition would often add references without the permission of Marvel and clearing them with their legal team. One example is the Hulk being featured in a newspaper clipping/computer screen. This had to be removed due to the character's rights still being held by Vivendi Universal.

In the PlayStation Magazine Issue #90 demo, Official Xbox Magazine Issue #40 demo and the trailer for the game, the Punisher is voiced by a different unknown voice actor. The demo released in PlayStation Magazine is dated March 2005, however the game was released in January 2005, and it was officially announced that Thomas Jane (who played the Punisher in the titular 2004 movie) joined the cast for the game in late 2004. This may mean that Thomas Jane voicing the titular character was a last minute decision.

After the completion of The Punisher, artist Frank Marquart and a smaller group at Volition began preliminary work on a sequel tentatively titled "Punisher 2: Sandbox Punishment", planned for release on the Xbox 360 and PlayStation 3 in 2007. The scope of the game was to move away from linear, hallway-like level design to instead having a more open world setting, incorporating aspects from the comics such as the Battle Van, and appearances from characters like Daredevil, Deadpool and Elektra. It's likely the plot would have followed the post-credits scene in the first game, featuring Kingpin preparing to enact revenge on the Punisher. The game that would later become Saints Row was being developed simultaneously, prompting The Punisher team to develop the game with an early build of the same engine Saints Row was using. Punisher 2 only spent a month and a half in development before being scrapped, though some of the vehicles and animations made from it would be carried over or reconsidered for the Saints Row series.

The final level of the game, Ryker's Island, is loosely inspired by the first issue of the 1986 Punisher comic miniseries written by Steven Grant, which began with the Punisher being tried and imprisoned on Ryker's Island and encountering Jigsaw while there. The game instead has the Punisher deliberately getting imprisoned on the island to defeat Jigsaw.

The game's manual is subtitled "War Journal" on the front cover. This is a reference to the 1988 comic book series "The Punisher War Journal", which was the Punisher's second on-going series.

During the level "The Takagi Building", one of the Yakuza members tells a story of a man named Sano, who took one hundred men, powered by MGH (Mutant Growth Hormone), to attack Daredevil. The encounter was said to have gone poorly for the Yakuza members, who were jailed or hospitalized. This dialogue exchange references volume #2 issue #57 of the comic book "Daredevil", where this event took place.