There are some clues as to what might appear. A leaked memo from Microsoft's Phil Spencer suggested that the company would “go big” with news about its Project xCloud game streaming service. If so, you'll likely have a much better sense of what it can do and when it'll be ready. The company also hinted at tidbits for people who “like watching others play games,” so you can expect some Mixer news.
The main unknown: hardware. Microsoft teased early work on new Xbox consoles in 2018 and is rumored to launch the systems (codenamed Scarlett) in 2020, so an E3 introduction might make sense. However, that all depends on whether or not Microsoft is ready to show its hand. Not that it might have much choice. Sony's PS5 teaser was arguably designed to steal Microsoft's thunder, and it might look bad if the Redmond team shows up at E3 with nothing to say about next-gen Xboxes.