The game's trading system differs from the previous editions in that weapons and armor that have degraded past a certain point are unable to be sold until they are repaired, at which point the repair costs usually offset the sell price. The Zone features a limited economy, with traders and inhabitants exchanging goods and services for money and items. If severely damaged or broken, a red HUD icon will denote this. The condition of an item is displayed as a gauge next to the entry in the player's inventory. Similarly, unmaintained weapons and some equipment will be damaged from continued use. Receiving damage will usually cause bleeding, which the player must take care of with medical supplies.

The majority of Call of Pripyat 's gameplay focuses on a combination of both post-apocalyptic horror, as well as tactical role-playing action. The game takes place inside the Chernobyl Nuclear Power Plant Exclusion Zone in Ukraine, divided into three areas known as Zaton, Yanov (including Jupiter and Kopachy), and ghost city of Pripyat.

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