In baseball this is the part of an individual's swinging range in which as a hitter they can make the best contact with the ball. If a pitch is right in your wheelhouse it is right where you want it, in the spot where you have the best chance of hitting it well.
The term is also often used to explain something that falls into a person's area of expertise.
ESPN: "Konerko can hit the ball 500 ft. if it's pitched right in his wheelhouse."
Child 1: "How can we get this hot girl to take her clothes off?"
Child 2: "Ask Hugh Heffner, that's right in his wheelhouse."
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