Discussions regarding a proper sequel to Marvel's Spider-Man began during the game's development, with open story threads for future titles being teased across both it and Miles Morales.

Peter and Miles can be freely swapped between at any point during free-roam in the game's open world, and have dedicated missions both in the main story and as part of side content that takes advantage of their individual traits.

During traversal, both Peter and Miles' new suits come equipped with Web Wings, which, when deployed, allow them to glide across the city, with their speed and distance covered increasing when taking advantage of areas such as wind tunnels.

The game follows Peter Parker (Yuri Lowenthal) and Miles Morales (Nadji Jeter), who both became the superhero Spider-Man after gaining superhuman abilities upon being bitten by genetically modified spiders.

Peter serves as a mentor to Miles, who gained his superpowers during the events of the first game, though he struggles with balancing his personal life and duties as the city's protector.

Other characters in the game include former New York mayor and Oscorp CEO Norman Osborn (Mark Rolston) and his son, Peter and Mary Jane's best friend Harry Osborn (Graham Phillips), who suffers from a neurological disease inherited from his mother, Emily;[11] Yuri Watanabe (Tara Platt), a disgraced former police captain and ally of Peter who has assumed the vigilante identity of "Wraith" following the events of The City That Never Sleeps;[12] J. Jonah Jameson (Darin De Paul), the Daily Bugle's chief editor and Mary Jane's boss; Danika Hart (Ashly Burch), host of the "Danikast" podcast; Peter's deceased aunt, May (Nancy Linari), who is featured in a flashback; and Miles' late father, Officer Jefferson Davis (Russell Richardson), who appears in a dream sequence.

Throughout the city, the two Spider-Men are faced with several supervillains such as Venom (Tony Todd), an extraterrestrial symbiote capable of bonding to human bodies and granting regenerative powers while negatively influencing their behavior; Sergei Kravinoff / Kraven the Hunter (Jim Pirri), the leader of a faction of mercenaries called the "Hunters" who seek to hunt super-powered beings;[13] and Cletus Kasady (Chad Doreck), also known as "The Flame", the head of a nihilistic cult who seeks to perform a demonic ritual to bring about an eschatological event dubbed the "Crimson Hour".

[14] Returning villains from the first game include Martin Li / Mister Negative (Stephen Oyoung), Mac Gargan / Scorpion (Jason Spisak), Lonnie Lincoln / Tombstone (Corey Jones), and Felicia Hardy / Black Cat (Erica Lindbeck).

Additional antagonists who were referenced in prior entries make full appearances in Spider-Man 2, including Flint Marko / Sandman (Leandro Cano), a lowly burglar who, through an accident, gained the ability to turn into molecules of sand and manipulate them at will; Curt Connors / Lizard (Mark Whitten), an Oscorp scientist who transformed into a giant reptilian creature;[15] Dmitri Smerdyakov / Chameleon (Jim Pirri), a criminal master of disguises and Kraven's half-brother; and Quentin Beck / Mysterio (Noshir Dalal), a visual effects artist and reformed criminal who became the head developer of a virtual reality entertainment attraction called "Mysterium".

The character Delilah, a skilled assassin who serves as the bartender at the Bar with No Name in an alternate universe, makes a cameo appearance during "The Message" side-quest.

[17] Peter starts his first day as a physics teacher at Brooklyn Visions Academy with Miles among his students, but they are interrupted by a rampaging Sandman, requiring both Spider-Men to subdue him.

While overseeing a prisoner transfer, a vengeful Miles fails to stop the Hunters from capturing Martin Li, who previously killed his father Jefferson Davis.

While visiting Coney Island to reconnect, Peter, Mary Jane, and Harry witness the Hunters attack the park to capture a reformed Tombstone.

In the aftermath, Mary Jane quits the Daily Bugle to run her own podcast and moves in with Peter, who opts to take a break from being Spider-Man to focus on rebuilding the EMF, trusting Miles to protect the city.

He likened the story's tone to The Empire Strikes Back (1980), contrasted with how Marvel's Spider-Man's narrative felt tonally similar to the original Star Wars (1977).

[11] Lowenthal discussed his portrayal of Peter Parker as he is under the influence of the Venom symbiote, citing "behaviors of addiction" as a major inspiration on how he would differentiate his two vocal performances at different points in the game.

[29] Intihar asserted that they never intend to interpret a character so differently from other appearances at the risk of alienating fans, but they did want to provide a unique take on the material that felt tied to their franchise, citing the creative liberties taken with Peter Parker's Advanced Suit in the first game as an example, and how despite the adherence to classic elements like the red and blue color scheme, the enlarged, white spider emblem on the suit's chest distinguished the character as Insomniac's version of Spider-Man among other adaptations.

[30] The game's gameplay reveal debuted during Sony Interactive Entertainment's PlayStation Showcase event in May 2023, highlighting a mission within the game's main story campaign that showed Peter Parker adorning the symbiote suit, and Miles Morales / Spider-Man, as the pair intercepted an attempt by Kraven's Hunters to capture Dr. Curt Connors as his transformation into the Lizard resulted in him breaking into a fish market near the New York City docks.

The sequence showed Peter Parker / Spider-Man initiating a takedown on a common thug using the spider-leg appendages equipped at the back of his new Advanced Suit.

[34] Intihar, along with producer Bill Rosemann from Marvel Games, Lowenthal, Jeter, Bailey and Todd, presented a Hall H panel at San Diego Comic-Con in July 2023, titled "Symbiotic Relationships".

[35] A gameplay overview narrated by creative director Bryan Intihar was featured as part of the PlayStation State of Play presentation in September 2023, in conjunction with preview events being held for media journalists in Los Angeles, where more extensive demos and playable builds of the game were showcased.

Taking place after the events of Miles Morales, the narrative features Peter Parker, Miles Morales and Mary Jane Watson struggling to balance their individual responsibilities and the former's respective duties to New York as Spider-Men, and features The Hood as its main antagonist, who is attempting to procure an allegedly ancient tablet inscrypted with magic tomes to resuscitate his dying mother.

This edition features two sets of five unique suits for Peter Parker and Miles Morales, designed by guest artists from PlayStation Studios and the wider entertainment industry.

It is a variant of the standard PlayStation 5 sporting custom face plates and a unique DualSense controller design based on the imagery of the Venom symbiote wrapping itself around a red gradient adorning Peter Parker's Spider-Man emblem.

Gene Park, writing for The Washington Post, applauded the development and increasing tension between Peter Parker and Miles Morales, as well as the former's friendship with Harry Osborn, noting that it was pushed as far as possible in a fashion that was "satisfying to watch.

[98] Intihar was questioned in the same interview regarding the potential to closely connect the studio's Spider-Man titles with the upcoming game Marvel's Wolverine, which he confirmed was set in the same shared universe.

Intihar stated he preferred that the Wolverine team remained committed to making the game stand on its own, but did not rule out crossing over the characters in the future as they had discussed earlier in development.

[99] Intihar was also asked about various easter eggs referencing Daredevil, namely the appearance of Matt Murdock and Foggy Nelson's law offices having been debranded and vacated after the events of the prior games, answering, "That's a good question.

[103] In December 2023, Insomniac Games was targeted in a ransomware attack by the group Rhysida, who published 1.6 terabytes (TB) of sensitive information concerning employee data, development assets and pre-production slates internally used at the studio.