Say "I'm sure ___" when you're making a guess about something and you're pretty confident in your guess. You can imagine that the confidence level of someone who says "I'm sure ___" is maybe about 70%.
When you say "I'm sure..." it often means that you want something to happen or hope that it will happen. Here are some examples:
I'm sure it'll be over by then.
I'm sure she's OK.
I'm sure we can work something out.