Fastest SSD/NVMe for an iMac (Late 2015)

If the external box is a Thunderbolt-3 device with its own power source then yes it would work.

• USB-C (USB 3.1/3.2) devices do not work with Thunderbolt-2, but can run at USB 3.0 speeds by connecting to a USB port.
• Thunderbolt-3 bus-powered devices usually don't work because there is a voltage/current bus-power mismatch between TB2 and TB3)

you are not going to get the ultimate speed externally you think you can. Read this article. If you can do it this is where the speed is going to be the best. I did this NVMe on my late 2015 MBPro and speeds were doubled. It write at 2600 and reads at 3100.

That's the simplest/cheapest option, yes, and probably all you need to revitalize a 21.5" 2015 with an anemic 5400rpm HDD.

However if you truly want maximum speed get an Akitio Thunder or Mercury Helios PCIe expansion box and drop an NVMe blade into an NVMe to PCIe adapter card.