Syberia II continues the adventures of American lawyer Kate Walker from the first game as she abandons her increasingly stressful life in New York in order to accompany an eccentric inventor to a remote land in Russia known as Syberia, where surviving remnants of prehistoric mammoths still live.
Kate begins at a small frontier town called Romansburg. With instructions from Hans' automaton train engineer Oscar, Kate is able to wind and load the train with coal. However, Hans falls ill and must be treated before they continue. From a little girl named Malka, Kate learns that the monks at the monastery on top of the nearby cliff can heal Hans. However, the old patriarch and his strict adherence to his personal rules forces Kate to jump through hoop after hoop just to get him to look at Hans. Worse still, the patriarch deems him a lost cause and figures that skipping straight to spiritual salvation is the best course of action. Kate learns from Hans about a friend of his at the monastery, who knows Youkol medicine. Though this man has died since, Kate obtains his notebook and makes an herbal candle to help Hans. The patriarch of the monks refuses to let them leave, but Kate improvises a sled from Hans' coffin to get him down the mountain. Things go from bad to worse when Kate is asked to fix some mechanical horses on Hans' behalf. Two thieves, Ivan and Igor, hijack the train while she works, intending to reach Syberia and make a profit from the mammoth ivory. Kate is able to follow them using a gangcar powered by a friendly animal resembling a cross between a seal and a bear.
Kate finally catches up with the train, but it collapses a bridge when it grinds to a halt, stranding Kate on the wrong side. Followed by the animal, which Kate names Youki, Kate works her way across a river, manages to avoid being eaten by a bear, and is reunited with her old friend Boris, whose flying wing crashes nearby. He lends Kate the use of the co-pilot ejection seat to launch her back to the train before Ivan and Igor can escape. Kate manages to make it to the train, but Ivan and Igor have given up on operating it and have left on a snowmobile with Hans as their prisoner. Kate and Oscar are forced to unhinge the passenger car to pursue the kidnappers. By the time they catch up, Ivan is off collecting ivory and the simple-minded Igor is having second-thoughts about the plan, as he is easily intimidated by the noise being made from wind blowing through a nearby statue. Hans has managed to escape his captors, but his whereabouts are as much of a mystery to Kate as they are to Igor. Kate stops the noise and convinces Igor to abandon Ivan. Kate confronts Ivan at a large mammoth statue surround by ivory. Ivan holds her at bay until she manages to convince Oscar to offer some assistance (blowing the train's horn) to create a momentary diversion. However, it doesn't completely succeed and Ivan is just about to kill Kate when the ice on which they are standing cracks, dropping Kate into darkness.
Kate awakes in the icy, underground village of the Youkol people. Hans is there, too, but he is on his deathbed. After convincing the Youkol people to help her drag the train inside, Kate makes her way to the shaman's hut. With the help of the shaman, Kate decides to reach Hans in his dreams and convince him to live. In the dream, set in Valadilène, Kate makes her way to the Voralberg factory, meeting young Anna and Hans' strict father, who says that Hans is locked in the attic as punishment. Using the clock to convince him it's time for work, Kate sneaks into the attic to talk to Hans. She convinces Hans, who alternates between his child self and his present self, not to give up. In response, he asks her to help Oscar "open up his heart." He disappears, and Kate touches an object on the table which ends the dream. When Kate delivers the cryptic message to Oscar, the automaton engineer knows what he must do: he will give his "life" for his creator, unlocking his hollow body to form a primitive exo-skeleton/life-support system for Hans. The key to the train and its final task are entrusted to Kate. There are no more tracks to drive on, but a frozen ship that will take them the rest of the way. Once Kate figures out how to get the train to thaw it, Kate, Hans, and Youki board the boat and set sail for the island of Syberia.
The journey is delayed by Ivan, who has stowed away on the boat. He attempts to leave Kate on an ice floe, but his inability to operate the vessel allows Kate to sneak back on board and raise the sails, simultaneously getting the boat moving and stranding Ivan on the ice floe. He unwisely decides to make one last show of defiance by tossing a penguin egg: the penguins do not take kindly to their nests being disturbed and kill him.
The ship reaches Syberia at last, but their journey is not quite over yet. The mammoths must be summoned for Hans to ride. Guided by an ancient medallion and some crude drawings on the ship, Kate manages to work out how to activate the Youkol horns and play the mammoth-riding tune. The mammoths are summoned and Hans goes to meet them. Still domesticated after all this time, they gladly let him up on their backs. The game ends with Hans riding one of the mammoths off into the distance, leaving Kate to wave tearfully, knowing she helped Hans fulfill his dream.