Truly custom or chopping around existing audio, and maybe injecting from another game?
Either way it is much the same as it is for any other system -- figure out the audio format, modify the format if necessary and edit the sound it wants to play. You will want the ability to decrypt 3ds ROMS, or have a 3ds ROM decrypted for you by something else. I do not know if this new hans stuff can be twisted to decrypt ROMs for you but you probably can get sorted there.
The 3ds, much like the DS before it and unlike most other consoles that are older than the GBA, has a high level format used by a lot of games (on the DS it was notable when another format was used, I have not seen or done something similar for the 3ds but from what I can see it is pretty similar). In hacking circles the format is usually known as BCSAR. Though that is the main archive format and the various formats it contains are the main things to do the actual deal (usually going by CSTM, CWSD, and CWAV).
http://3dbrew.org/wiki/BCSAR has a tiny bit on it all.
https://gbatemp.net/threads/release-every-file-explorer.373615/ will help a bit in this as well.
Smash brothers in particular has had a lot of people chopping it around and it uses a slight variation on the theme mentioned above. I should also mention BRSTM if you are dealing with smash brothers, and if you go looking you will probably find a lot of people talking about the related formats seen on the wii (things like BRSAR) and wii u as it is all pretty closely related.
There are some fairly nice tools to aid in this modification/conversion, afraid I am not quite up to date on the current stuff but
https://gbatemp.net/threads/release-brstm-bcstm-conversion-tool-beta.378702/ should provide you a nice jumping off point there.
Afraid I am a couple of weeks out and have missed the new hans stuff, looks like I will have to do some reading. However it seems smea has deviated from previous mindsets and has enabled some kind ROM hack support out of the box, I imagine it would have been better if you were on 9.2 or earlier but you probably can get something done and if you are using hans will need the original game (or I guess a sky3ds might work). It looks like you enable it in hans and tell it to read the either the modified parts of ROMFS or the binary side of things from the SD card instead.
Anyway I have said not a lot and I find myself with out of date knowledge, hopefully I at least got you started.