dtgreene: Edit: I'd also like any advice that you would give in almost all circumstances.
I may potentially be overspecialized and potentially couldn't give "general" advices.
If I would start to give you any I would likely send you on a venture of disecting your entire system.
B1tF1ghter: Unfortunatelly, unless you want comically long list, your description is way too superficial.
There is nothing I can toss you for starters as the issue could be caused by like a billion of various things.
Without solid specifics there isn't much of troubleshooting unless you like wasting time for testing totally random stuff with correlation to nothing (because with this level of details that's about all that can be given to you).
dtgreene: Could you maybe ask a question that might help troubleshooting this?
I can give you some questions to get the general idea what is the magnitude of the problem and potential complexity of the solution.
Tho the first thing I'm going to ask is this:
-1. how urgent is this? Do you want this done within a week or can you afford stretching it into 1-2 months?
This is a serious question as I am going through many depths of hell in my IRL life atm (I was before, and over time it's only getting worse so far) and so I will definitely not be able to help you troubleshoot this within a singular week if the issue is too complex.
So:
0. driver type, mesa or something official, if official then what exactly (there are few different official amd drivers)
1. what are you using for vulkan, is it radv or amdvlk (or else)
2. dxvk version
3. define "performance issues", what is it? Stuttering? More non-spike fps drops? More noticable fps drops in specific situations?
4. when was the last time you updated your gpu driver in relation to when the problem started occuring (this is related to shader cache which gets rebuild from scratch after each mesa update)
5. storage device used (hdd, ssd, others, depending on what it is and what else loads it during gameplay it could potentially be a bottleneck during new areas load-in causing issues)
6. amount of ram available total in system
7. when you start the game how much ram do you have free on average (real free, after accounting for buffers and cache)
8. cpu performance governor used during game
9. do you use p states on the cpu
10. do you use SMT on the cpu
11. do you use dynamic boost frequency on the cpu
12. did you try running just the game and nothing else at the time, if so did the issue persist
13. do you use compositor (in DE / WM), if yes then do you run it while playing the game
14. x11 or wayland? Or xwayland?
15. did you change nice level of literally anything
16. what audio backend do you use: pulseaudio, alsa, jack, jack2, oss, other ones
17. did you change your audio backend settings
18. do you use realtime kernel patches
19. mouse polling rate (yes, this is rather major issue, tho wine devs appear to ALWAYS deny that it's de facto THEIR code's issue and refuse to fix the related thing)
20. do you use freesync with the game
21. do you use multi-head (multiple screens)
22. this is a laptop I presume? (mobile chip itself doesn't warrant that as there are some IoT boards with these) Do you have issues with cooling by any chance?
23. do you play the game with psu connected
24. is the issue consistent over time or does it get worse during prologned gameplay sessions and / or long system uptime
25. do you have swap, if yes then how much, what type (file, partition)
26. do you use disk encryption
27. do you use file indexing on the system
28. do you have any cron / scheduled jobs
29. file system used on the drive hosting the game, and did you use any non default mount flags in fstab
30. has the issue always been there or did it start recently
31. are you connected to any networks during the gameplay
32. when the issue happens does the audio get out of sync or not
This is for starters. As I said with such low amount of info I could give you comically long troubleshooting list, with this above not being even a "start" of it.