During the investigator's turn, the keeper may play mythos cards to attempt to injure the character physically or mentally, degrade or destroy their items, or otherwise set them back.

The expansion also contained four new investigators (Carolyn Fern, Dexter Drake, Darrell Simmons, and Vincent Lee), four new monsters (two byakhees and two crawling ones) and six new map tiles as well as additional cards and tokens.

This expansion aimed to shift the game's focus to outdoor settings that were designed to be less linear to give players more choice in exploration and investigation.

[4] Aside from some minor modifications, gameplay was fundamentally the same as in the first edition but with the role of the keeper replaced by a companion app that would run through Steam on Mac or PC, Apple iOS, or Android platforms.

Players who owned either the first edition base game or added the Recurring Nightmares figure and tile collection could play an additional scenario.

Players who owned the first edition Call of the Wild expansion or added the Suppressed Memories figure and tile collection could play an additional scenario.

The Recurring Nightmares Figure and Tile Collection contained game components from the first edition base game—eight investigators (Jenny Barnes, Joe Diamond, Gloria Goldberg, Sister Mary, Michael McGlen, "Ashcan" Pete, Harvey Walters and Kate Winthrop), eighteen monsters (four Zombies, two Chtonians, two Cult Leaders, two Hounds of Tindalos, two Maniacs, two Mi-Go, two Witches and two Shoggoths) and fifteen double-sided map tiles.

The Suppressed Memories Figure and Tile Collection contained game components from the Forbidden Alchemy and Call of the Wild expansions—eight investigators (Monterey Jack, Bob Jenkins, Amanda Sharpe, Mandy Thompson, Dexter Drake, Carolyn Fern, Vincent Lee and Darrell Simmons), fifteen monsters (two Children of the Goat, two Dark Druids, two Goat Spawns, two Nightgaunt, two Crawling Ones, two Byakhee, one Wizard, one Dunwich Horror and one Dark Young), and seventeen double-sided map tiles.

The Beyond the Threshold expansion was released in January 2017 and included two new investigators (Akachi Onyele and Wilson Richards), one new monster (four Thralls) and six new double-sided map tiles, as well as additional tokens and cards that expanded the base decks.

[8] The Streets of Arkham expansion was released in the fourth quarter of 2017 and included four new investigators (Finn Edwards, Diana Stanley, Tommy Muldoon and Marie Lambeau), four new monsters (two Star Vampires, two Skeletons, two Hired Guns and one Lloigor), and seventeen new double-sided map tiles, as well as additional tokens and cards that expand the base decks.

[9] The Sanctum of Twilight expansion was released in the first quarter of 2018 and included two new investigators (Lily Chen and Charlie Kane), one new monster (two Wraiths), and five new double-sided map tiles, as well as additional tokens and cards that expand the base decks.

The Horrific Journeys expansion was released in the fourth quarter of 2018 and included four new investigators (Agnes Baker, Jim Culver, Silas Marsh and Trish Scarborough), four new monsters (two Warlocks, two Dimensional Shamblers, two Hunting Deep Ones and one Formless Spawn), and eighteen new double-sided map tiles, as well as additional tokens and cards that expand the base decks.

The expansion unlocked the three new scenarios — "Murder on the Stargazer Majestic", "10:50 to Arkham" and "Hidden Depths" taking place on an airship, a train and a cruise ship.

Both the first and second editions of Mansions of Madness received favourable reviews at Eurogamer,[20] Penny Arcade,[21] Board Games Land,[22] iSlaytheDragon[23] and the Dice Tower podcast.