I have one big network with 1300+ depots total and at least 3k drones in this network. There is this problem I found out - drones tends to stuck on load/unload/starting trip. They just hang out on depots with their pals, sharing tales about other depots, I guess, before taking off - usually they are stuck for few seconds. I noticed this weird behaviour in last 15-ish hours of game, when my number of depots and drones kinf od blew up (pretty much doubled over the course of ~20 hours of ~100h of total game time. I'm running it with Krastorio2, on stable 60 UPS all the time. I observe this on depots where path is one tile wide (they all sit by road, just one tile away from it), on depots with very wide path, and on depots directly connected to road - so all types I currently have in base. It isn't particulary annoying, since they get their job done in the end and it isn't hurting throughput that much usually, but it is something that just catches they eye, when most of the drones are stuck on starting depots for up to 20s.
Now, I wonder - is this something purely mod related or it is just pathfinding being wonky and trying to recalculate paths for tousands of drones at once a tad too slow?

Similar issue here. Drones chilling in request depots. I have an empty request depot stocked with 20 drones and plenty of fuel... only two of the twenty actually bother to go get items from a max stocked supply depot. this is a much smaller base than the above comment. a few hundred drones at most and 40-50 depots.

EDIT :: nevermind, fuel issue, i ran out of crude.

I found one of my limiting factors was not having enough supply depots. I think the requestors would only send out as many drones as they could currently see resources in the transport network, not tracking input flow or being able to tell about my buffering outside of the road network. I switched from having 1 oil supply depot per patch to 5 and my 30 drones all decided to head out and move things instead of only one or two. Might be running into something similar at your larger scale?

Nah, it's not the problem with supply depots. I think it's pathfinding - drones are sent out properly, but they got all funky when they arrive at depots. They just chill out, like trying to figure out how to come back to home. When I stopped my base from running at full capacity, everything went to normal, but as soon as I start researching things and items get moved around it gets still laggy once again. It's not problem with providers, it's problem with big queue for pathfinding, I guess. Still, when I made few buffer zones with a lot of buffer depots to move everything into one place, effectively shortening path for most of drones, the issue isn't as severe as before, but once again - a lot of drones makes other drones sit at depos.

It is probably the path finding algorithm being having to do a more costly pathfinding on 1-wide roads. So as to not block the game the pathfinding is probably capped affecting all units. According to https://mods.factorio.com/mod/Transport_Drones/discussion/5ea54a577ed351000f1bfba0 you should always have at least 2-wide roads.

Road are 4 tiles wide, with extra tile for depot (it sits inside the cell) - looks like that: https://imgur.com/Gcr9pA7 . It's just there is so many drones, it just takes too long to recalculate paths. After expanding a bit, I have 1.9k depots with around 20k drones (total production, extra 1k is sitting at mall) https://imgur.com/yYmNQsF plus few mining outposts. Tried doing drones only base, buuuut it's kind of hard when pathfinder takes more and more time and causes chain reaction of slowdown. Cool mod anyway, had a blast:)

Can you provide your save game? I can try to do some optimizations

Sure thing! Where I should send it?

You can attach it here, or send it to me on discord

https://drive.google.com/file/d/1kuLTTLlbFaYLOizO6p4d-KJuurFvXt0w/view?usp=sharing
Just uploaded it onto google drive:) Is that okay? Basically, you need only to start research to make things funky, I think.

Hmm, seems the pathfinder is at its limit, I will bump it with the mod , until then you can use a console command to increase the path finder limit:

/c game.map_settings.path_finder.max_steps_worked_per_tick = 10000

Thanks a lot for your work!:) It was enough, to make things smooth once again:) Was about to switch to train based base, but it seems I can have more fun with drones :^) Once again, thanks for a mod!