Metro Exodus is a first-person shooter game with survival horror and stealth elements. Set in the post-apocalyptic wasteland of the former Russian Federation, the player must cope with the new hazards and engage in combat against mutated creatures as well as hostile humans. The player wields an arsenal of hand-made weaponry which can be customized through scavenging materials and a crafting system. The game features a mixture of linear levels and sandbox environments. It also includes a dynamic weather system, a day-night cycle, and environments that change along with the seasons as the story progresses. It will be set over the course of one whole in-game year.

[section title="Plot"]
After the attack on D6 in Metro: Last Light, Artyom becomes disillusioned with the constant infighting and corruption within the Metro and leaves the Spartan Order. He soon becomes obsessed with proving that other human survivors exist outside of Moscow and makes numerous dangerous expeditions to the surface, much to Anna's concern and Miller's frustration. However, on one such expedition with Anna, they witness a working train running on the surface. Before they can follow it, they are captured by Hansa soldiers, who have also captured other prisoners who reveal they come from outside of Moscow. The Hansa soldiers execute the outsiders and Artyom is shot and left for dead when he tries to intervene. Surviving the gunshot, Artyom follows the soldiers to their base to rescue Anna, and in the process inadvertently destroys a signal jammer that was blocking all communications going in and out of Moscow. Radio transmissions from all over the world begin being picked up, and Artyom and Anna realize humanity hasn't gone extinct. Yermak, a train engineer working for the Hansa, agrees to help Artyom and Anna, and the three of them escape by stealing one Hansa's trains.

As the train leaves, the Spartan Order moves in to retake it and are shocked and confused at Artyom and Anna's presence, with Anna accusing Miller of being complicit in Hansa's coverup. Knowing that Hansa will have all of them put to death for knowing the truth, Miller concludes that the Spartans' best chance of survival is to flee Moscow. Once outside the city, he reveals to the others that while many of Russia's cities were bombed, the war did not end and NATO proceeded to occupy what was left of the nation. In order to prevent more bombs from being dropped on Moscow, the Russian leadership decided to secretly jam all communications to make the outside world believe nobody had survived. They then receive a radio broadcast from Moscow Defense Command calling for survivors to rally at the "Ark" located at Mount Yamantau and Miller decides to head there, believing that the Ark is where the Russian government has rebuilt itself.

The Spartans proceed to Yamantau, battling bandits and religious fanatics in the process while also picking up additional survivors. They finally reach Yamantau, but quickly discover that the remnants of the Russian government have devolved into cannibals luring survivors in with the false promise of safety. Artyom and the Spartans manage to fight their way out and escape, but Miller's faith in Russia is shattered and everybody is left wondering what to do next. Using a map they recovered from Yamantau, they decide to travel to a satellite communication center near the Caspian Sea in the hopes of gaining access to a satellite to find habitable land to settle. At the dried up remains of the Caspian Sea, the Spartans steal much needed water and fuel from the local bandits and free their slaves while obtaining an updated satellite map.

As the Spartans continue on their journey, Anna begins to cough up blood, fearing the cause was accidentally breathing poison gas during the journey. They decide to scout a nearby forest valley to see if it is suitable to settle. While scouting the forest, Artyom is caught between two rival survivor factions who are both terrorized by a giant mutant bear called the Master of the Forest. However, he also discovers that the dam protecting the valley from radiation is on the verge of failing, making the area unsuitable to settle. Artyom is able to defeat the Master of the Forest and return to the train, but Anna's condition has worsened. The only chance to save Anna is to find the antidote in Novosibirsk, but the entire city is heavily irradiated.

Miller and Artyom decide to head into the city alone to search for the antidote despite the risk. They enter the Novosibirsk metro and find a young boy named Kiril, one of the last of the Novosibirsk survivors. Kiril explains that his father left on a mission to obtain a map marking the location of a clean, habitable area. Miller decides to go find the map while Artyom heads out to find the antidote. However, as he proceeds deeper into the city, he begins experiencing vivid hallucinations. Artyom manages to recover the antidote, but is gravely wounded by a mutant and absorbs a heavy dose of radiation. Artyom, Miller, and Kiril return to the train with the map and the antidote, but Miller dies of radiation poisoning on the way back. The rest of the Spartans donate their own blood to give Artyom a critical blood transfusion. Anna is cured with the antidote and with the map, the Spartans settle on the shores of Lake Baikal, which is free from radiation. However, Artyom's ultimate fate depends on the choices he made during the journey.

In the bad ending, Artyom dies from the radiation poisoning, and the Spartans and a grieving Anna hold a funeral for him and Miller. In the good ending, Artyom manages to survive. Miller is buried and Artyom is selected to take his place as leader of the Spartan Order. Now that they have a home, Artyom decides that it is time to search for other survivors.