Yes, with regard to meaning. No, from the point of view of grammar. 'In spite of' and 'Despite' are prepositions and do have the same use and meaning. They are followed by nouns e.g. In spite of the weather... Despite the difficulties... In spite of his age .. 'Though', or more commonly 'Although' or 'Even though', are conjunctions. They are followed by verb phrases e.g. Although it was raining.. Even though there were problems... Though he was very young...

"In spite of" and "despite" have the same meaning. The next thing that follows is a noun, or gerund. "Although" is followed by a statement.

In almost all cases, yes.