It pays to check out the official instructions, but I will point out that USB sticks are prepared differently for Legacy BIOS vs. UEFI even without Safeboot. For example if you run Microsoft's Media Creation Tool to create Windows installation media using a UEFI machine, then the USB stick will be formatted as GPT which will not boot on a Legacy BIOS machine. For WinPE a USB stick that can boot both must have both a \boot folder for the Legacy boot files and \EFI for the UEFI boot files. And many older machines have a capacity size limit for USB sticks they can boot from too, so 32GB or less is more universal.
All these compatibility issues could be avoided by using a USB optical drive instead, which should boot on any machine that lets you select booting from USB. But of course that would limit how many tools you can include to 8.5GB per disc for DVDs. It is apparently possible to make bootable Bluray discs too, but I don't know if every PC can boot from those, especially those 100-128GB BDXL ones.