Specifically with Shimano:
I've run mix & match for years - my current tourer is 3x9 speed, with flat bars, deore shifters, and deore crankset. At the back is tiagra GS rear mech and 12-27 cassette.
Previous tourer was 8 speed, with Sora 8 speed STI road levers on drop bars, sora front mech...