The per-PCB cost of manufacturing a small number of PCB is 10 times or more compared to the per-PCB cost of manufacturing a large number of PCBs.
So what is it exactly that adds to the cost?
People say there is setup cost or initial cost, what is it exactly? What steps in manufacturing need a special setup and cost this much?
I know there is printing of transparent film, but is it that costly?
Firstly the manufacturer needs to check your uploaded board for any irregularities. This is done by hand by engineers, so will cost a fair bit. If it is checked, the manufacturer needs to send your uploaded board to the place where production happens. Each batch of boards all need to be tracked, need their own place in the chemical baths, and need their own setups for the drilling and milling machines. I can imagine swapping batches takes longer than continuing to the next board, so that adds to "initial costs". At last you have packaging, individual packaging is a bit more expensive (per board) than packaging large batches.
Your questions is somewhat vague. What is "small number"? What is "large number"? Making onesies is always going to be expensive, but when using PCB batching services at least you're not paying fixed upfront costs. Typically you are charged per in² of PCB space, with some extra for premium features like more copper, finish, etc.
However, to contrast really-low-volume (onesies) to really-high-volume (millions) you need to consider that there are different manufacturing techniques as well - where the board is punched, not drilled, and is made of phenolic resin, not fiberglass. This answer explains it fairly well.
This technique is specifically made for very high-volume production, and you just cannot use it for onesies.
On a somewhat related note, you may have noticed that, if you are small electronics manufacturer, on several ways you just can't compete with the big guys. Newcomers aren't welcome: they don't have the resources to set up automatic assembly lines, to use the really-high-volume PCB production processes, to twist the hands of overseas slave manufacturing, or even patent their work (with a single patent ~€10k, and that's for EU only; don't get me started if your gizmo has radio and needs FCC testing in the US).
OK, so you resign to making small batches of niche products, in this case likely the expensive PCBs may not be your biggest gripe. What startled me sometime ago was how costly custom plastic enclosures are. If you can fit your product into a standard box with drilled holes, then you're good to go, even though you need to tailor your PCBs to the existing enclosure. Big guys aren't constrained to that, since the $5k cost for a mold matrix is nothing to them. And they exploit that, because consumers value custom and sleek enclosures, they are viewed as "professional".
All in all, the industry begs for disruption, but I would not start with the PCB side of it.
Even if you consider logistics alone, that custom PCB you want in a single-digit quantity is a separate product. It has to be produced, tested, stored, shipped and billed separately from other products, otherwise you will not get what you ordered. At every step there will be some fixed costs which would not apply if the factory had to produce another 10 pieces of an existing PCB.
If you produce a million of PCBs, you can set up an automated testing stand and a packaging robot. The 10 PCBs you ordered will certainly require human involvement.
