Normally Sasuke would win with low difficulty but in this case, I guess mid difficulty since Tsunade can tank susanoo attacks. Still once Sasuke encases her within a susanoo arm, she'll be crushed completely with or without regeneration. Also note that Tsunade can't destroy a full formed susanoo and even without it, Sasuke can predict her movements with the sharingan. He is also much faster than her and can slow her down even further with genjutsu.
I guess susanoo arrows can blow her head off or once Sasuke preps kirin, he can obliterate Tsunade.