The second part of City Slickers begins after the death of Curly. It is the 40th birthday of Mitch Robbins and the day begins quite good until he returns home (after a hard day at the radio station) and finds his brother Glen, the black sheep of the family, in his sofa. Nevertheless he is about to have a wonderful birthday-night with his wife when he discovers a treasure map of Curly by chance. Together with Phil (from the first part) and unfortunately with Glen he tries to find the hidden gold...

Mitch is a middle aged big-city radio ads salesman. He and his friends Ed and Phil are having mid-life crisis. They decide the best birthday gift is to go on a two week holiday in the wild west driving cattle from New Mexico to Colorado. There they meet cowboy Curly who not only teaches them how to become real cowboys, but also one or two other things about life in the open air of the west.

On a red eye flight to Boston from LA 10 people wake up to a shock. All the passengers and crew have vanished. When they try to contact the ground they make no connections. They land the plane only to discover that things haven't changed. But its like the world is dead. No one is there, the air is still, sound doesn't echo, the food is tasteless. And a distant sound is heard coming closer. A race of monstrous beings bent on their destruction is heading for them, eating everything in sight.