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Using the handcannon with infinite ammo with pistol riffles and shotguns should have been an easy win for you. Just pump its damage and thats it. Use it for bosses and taking care of tough enemies.
I saw people said it sucks, so I just want to try it out, at first its quite ok, but later on it just not perform well, let say the Right Hand boss, after his hp go down he still start standing and keep go up and down to avoid your headshot, which means he can able to hit you if you miss your Handcannon, which for Chicago it wont be problem, you just move along with his head and he get stunned the entire time.
I literally did Professional S+ with infinite Handcannon with zero problems.
Saved at Castle 7, before making any decisions: Chicago Sweeper felt way too spammy, brainless, and inaccurate during my Hardcore S+ run so I went the Handcannon route and I'm glad I did; dropping piggies and chainsaw wielders in a couple of hits is too satisfying, also penetrates through targets, I balled a scoped Sentinel to take out eventual archers/bazooka bois with, you don't even need it against the wrench man except to find out which has one it, Handcannon decimates those fatties with parasites inside them too (Biosensor Scope ones), the Sweeper does not.
You should keep a scoped Sniper when you REALLY need to be accurate (Puzzle Targets, Archers, Bazooka / Dynamite throwers etc, also for the Wrench), this is something you should probably do even if you go the Chicago route.
capcom knows exactly what they are doing because they want to sell unlock dlc. you have to get an S+ in professional to get the cat ears and the cat ears can be used to get S+ in professional. its intentional just like the infinite ammo box in resident evil 2 remake where you couldnt get S+ with infinite weapons but the exception was the infinite ammo box because it wasnt a weapon and gave all weapons infinite ammo. They do this crap to make money off of completionists that cant beat the difficulty and theres alot of them.
Might be annoying, but anything the Handcannon does hit will stay down.
Also just bring a Stingray with you, use it for long range targets if needed, ez.