Though the exact location and date are never mentioned, it is very heavily implied by character dialogue and environment clues that the game is set during the Russian Civil War.

[7][8] The world of Pathologic 2 leans heavily into the surreal, meta-commentary and symbolism, frequently making discerning what is fiction and what is "reality" difficult.

The player's "reality" often comes into contact with this framing, with theater-like elements such as spotlights, "scene changes" between day and night and a disembodied stagehand-like voice appearing intermittently throughout the game.

Nearby strangers in plague doctor suits tell him that the locals suspect him of killing an important resident of the town and that the attack on him was an act of revenge.

He is urged to accept his father's legacy as a menkhu, a special caste of Kin folk with the right to cut open bodies.

Signs of an outbreak appear in the village, including a strange rot on the sides of buildings and a black cloud in his father's old bedroom.

A plague known as 'Sand Pest' strikes the town, killing people within a day of infection and leaving the districts abandoned and rife with looters.

It is revealed that the Sand Pest has hit the town once before, and Isidor managed to curb the outbreak by boarding up the infected district and leaving all those within to die.

Artemy is able to use his father's old equipment to create tinctures that increase immunity, and later use organs or blood to produce antibiotics and painkillers.

He continues to search for larger amounts of sacred blood, eventually learning that the only way to get enough to stop the plague is to destroy a tower known as the Polyhedron.

The mysterious 'udurgh' refers to the Earth itself, which is leaking out the sacred blood due to being repeatedly harmed and nearly killed by the Town's presence.

Destroying the Polyhedron will produce enough of this blood to cure everyone, but kill the Earth in the process, causing many of the 'miracles' of the world - including many aspects of the Kin - to fade and die.

Gameplay in Pathologic 2 takes place primarily in the Town on the Gorkhon River, with occasional diversions for tutorial sequences and other one-off events.

The town is divided into a number of districts named after various body parts, such as 'The Gut' or 'The Hindquarters', which may become infected or abandoned throughout the game as a result of the plague.

During the day, most things will be available for the player to pursue and townsfolk will take part in their daily activities (as long as the district is not infected); shops will be open, children will be playing in parks and on streets and citizens will move around the city.

The player is able to obtain items in three primary ways; they can be purchased from shops or merchants, bartered for with townsfolk, or found in containers in the game world.

Better items can be found inside houses, but getting to them requires either committing burglary and possibly becoming hated by the community, or breaking into an abandoned home that has been infected with the plague.

Organs sell for very high prices and can be sometimes useful, but the process involved in obtaining them is frowned upon by the town, causing the player to lose their trust if it is done too many times.

The player must manage a variety of needs in order to stay alive, including hunger, thirst, exhaustion, health, immunity from the plague and their reputation with the areas of the town.

Hunger can be sated with food, which becomes significantly more expensive and rare the longer time progresses due to the plague and an absence of supplies from the train network.

If the player's immunity drops to zero, they become infected with the plague and must consistently treat themselves with antibiotics to avoid dying until a cure is found.

For example, performing an autopsy on any body, even a criminal, will harm the player's reputation with the town until they permitted to do so by being declared a "menkhu," a type of religious healer, by the local religion's elders.

Curing citizens of the plague and containing the spread of the disease is not always possible, but attempting to do so can open up new opportunities for the player and successful actions as a healer or helper will greatly improve their reputation with the town.

As the Haruspex, the player is given access to a factory building which allows them to mix various herbal tinctures and other types of medicine, which can be used to cure infected people of the plague.

Various plants that grow on the steppe can be mixed to create tinctures that allow the player to "sense" disturbances in any one of these bodily layers when healing a person.

Successfully healing citizens will substantially improve the Haruspex's relationship with the town, and he may be referred to or officially declared as a "menkhu," or "cutter," a type of religious healer that is permitted to perform various restricted procedures.

[17] On 6 July 2020, Ice-Pick Lodge announced that they were working on the second of three promised scenarios, "The Bachelor", stating it is to be released "in the foreseeable future.

"[18] On 7 July 2022, Ice-Pick Lodge made a post on their Teletype "About the studio and it's projects" discussing what they have been working on such as Known by Heart and Franz but most notably the Bachelor route, the second playable character coming to Pathologic 2.

[20] On 2 January 2024, the pitch for the Bachelor route of Pathologic 2 was leaked on a Readymag site,[21] but the page was taken down shortly after the link started circulating[citation needed].

[22] On 7 October 2024, it was announced that the Bachelor's route would instead be released in 2025 by HypeTrain Digital as a standalone sequel, Pathologic 3, with a dramatically different gameplay and scope and will feature time travel as a major element.