TLXOS won't boot! What's wrong?

Have you turned Secure Boot off?  TLXOS does not support Secure Boot.

There are some other known issues - we'd mostly argue they are BIOS bugs - with certain UEFI BIOSes.  Known offenders include Dell Optiplex models, Intel Compute Sticks, and certain NUC models (mainly the more recent ones, plus the notoriously buggy DE3815TYKHE).  Issues and possible workarounds may include:

• When using TLXOS 4.x, the BIOS may not action attempts by the TLXOS installer to change the default UEFI boot order using efibootmgr; on the original Falls City Compute Stick (STCK1A32WFC) this may even crash the BIOS(!).  Consequently, after the install completes you may need to enter BIOS setup and manually set the correct boot device.  Dell Optiplex BIOSes may have this problem.
• Upgrading from TLXOS 4.x to 5.x may confuse UEFI BIOSes by neglecting to delete the former Maintenance Mode boot entry, depending on how smart they are about invalidating existing boot entries and auto-adding new ones.  It may therefore be necessary to enter your BIOS and manually reconfigure the correct boot device after upgrading to TLXOS 5.x.
• Leaving the PXE boot ROM enabled may clash with the Syslinux boot loader, particularly on NUC BIOSes with boot-from-iSCSI support.  This is likely to be some kind of low memory contention problem, i.e. the BIOS uses too much memory, and overwrites RAM that Syslinux is using, or vice versa.  Unless you are actually using PXE boot, enter BIOS settings and set the PXE boot ROM to Disabled.  The same may also be true of other unneeded BIOS features that are enabled by default.
• Turning off UEFI boot may prevent Legacy booting of TLXOS because the BIOS doesn't understand GPT partitioning unless UEFI booting is enabled, and (erroneously) pre-emptively decides that the GPT-partitioned TLXOS boot device is unbootable and won't even try to boot it.  This is a common failing of Intel NUC BIOSes.
• On Intel NUCs and Compute Sticks, booting a non-default device using the F10 option may not work, for unknown reasons.  You therefore need to enter BIOS setup using F2 and configure it such that either the USB stick appears first in the UEFI boot order, or select the "boot USB device first" option.
• Certain Dell OptiPlex and and Lenovo ThinkCentre BIOSes will not boot TLXOS in UEFI mode for unknown reasons.  You may need to configure your BIOS to boot in "Legacy Only" mode; do not use "Legacy First" (mixed) mode, as that probably won't work either.
• Some very recent BIOSes (e.g. a MeLe Quieter 4C that I recently bought) claim to have Legacy (CSM) boot, but this doesn't fully work (e.g. no video output).  Apparently some BIOS developers no longer understand/care how Legacy boot works, and pretend to provide this only for marketing reasons.

To avoid having to support multiple bootloaders, ThinLinX uses the Syslinux family of bootloaders wherever possible (it isn't possible on the Raspberry Pi, and we also had to tweak our ISO images to use rEFInd for UEFI DVD boot).  Syslinux is unpopular and now largely unsupported, and most Linux distributions use GRUB 2 instead on x86 hardware.  On non-x86 hardware, there is no bootloader that will work on everything, although uBoot comes close (unfortunately its Raspberry Pi support remains imperfect).

Unfortunately Syslinux doesn't work reliably with all UEFI BIOSes, and as it is no longer being developed, no fixes are available. We've already explored alternatives such as systemd-boot (formerly Gummiboot), but with the possible exception of GRUB2 (which we don't want to use on account of its complexity), they appear to have the same problems.

TL;DR: x86 hardware developers only care that their BIOS will boot Windows, Ubuntu, and CentOS/RHEL, and don't care about anything else, which may be a problem for other operating systems (including TLXOS).