Hi, this is the first time I haven't been able to get a game to run.
I'm running Win7 Home Edition 64 bit, nvidia gtx 280 1gb, 8gb ram, creative X-Fi extreme gamer sound card.
I have tried every compatability setup there is also tried with and without "run as administrator" and all I get it the initial Microids opening flash screen for about 2 seconds and the it just stops. I even checked the task manager and it shows that there is nothing running.
I also tried uninstalling it and then reinstalling it 4 times, no joy.
I also deleted the files and re-downloaded them again even though they passed the integrity check.
I get an initial error when launching right after installation, see attachment. (this happens everytime after install and before you say anything remember I already have uninstalled and redownloaded multiple times). Also, this only happens when I use the LAUNCH button on the gog install screen after the game has finished installing. I don't get this error message when I launch from the desktop icon.
Anyone got any constructive ideas, anything that I haven't already tried will be welcome.
Also there is a "launch" folder with some strange entries and it seems to launch the splash page, but that's all. A screenshot of the settings.ini file in the launch folder is attached.
btw, I love this site, I have over 50 games from here now.
Tlhanks for your time
EDIT: thanks Stuff but I already tried everything you mentioned. Also I have never even played any game called MegaRace. That folder is actually used by the game.

I don't have Amerzone but since you have gone 4 days without a response I will offer a suggestion. . . =)
All the files for the game should be in C:\Program Files\GOG.com\Amerizone. The image you have attached appears to be a leftover file from a Megarace install and should not be associated with or affect the Amerizone install, IMHO.
I would first check out the solutions listed on the game support page. Might help . . . =)
If not, since you have tried most everything, I suggest you uninstall the game, deleting any directories / files that are remaining after the uninstall under Program File\GOG.com\Amerzone and do a fresh install in a directory outside of Program Files.
Turn UAC to Never notify.
Create a directory outside of Program Files, something like C:\Games. Right click the setup.exe and click "Run as an administrator" in the resulting dialog. On the first dialog of the GOG installer, click the Options button on the lower left corner and point the install to the Games directory.
After install, right click the game shortcut, on the resulting dialog click Properties, click the Compatibility tab, check "Run this program as an administrator" and uncheck the compatibility mode. You may need to use that but I would start without any compatibility mode selected.
Set UAC back to it's default setting. Try the game. This should eliminate some standard run issues with Win 7.
You might try using RunFirst to set the affinity to a single core if the game starts after the reinstall. Setting the affinity to a single core on multicore systems sometimes clears up some graphics problems.
You can do it manually by starting the game, ALT-TAB back to the desktop, open task manager (CTRL - ALT - DEL ), find the [game name].exe on the Processes tab, right click the exe and click Set affinity . . . on the resulting dialog. Un-check all but the CPU 0 check box. Close the task manager and play the game. If this helps I suggest using RunFirst as it sets the affinity for the game without having to go thru the task manager process each time you play.
Some games need the memory limited on Win 7 64 bit systems but that is a pain since you need to do it each time the game runs and undo the limit when you close the game. If all else fails I will post an image for the procedure . . . =)
You should open a help ticket with GOG support as well.

I'm having the same problem. I noticed the MegaRace thing in my own settings.ini, and I tried changing that to the directory my Amerzone is installed to, but that only made things worse. With that, trying to run the game didn't even show the splash screen, but instead opened an AutoRun error window (screenshot attatched). I'm not sure what this means or how it could help, but it seems to be related. Changing the settings.ini back to its original state made the game launcher behave as it did previously - open a splash screen for a few seconds then nothing.

Stuff: jmarsh07 and Grandolin are right, the .ini file does indeed have references in it to MegaRace. I don't know if GOG got the wrong .ini file with the game, or whether this is actually what Microids distributed with the game.

I get the Microids splash screen, but after that, my screen goes black, and nothing I do with the keyboard will invoke a response (not even <Ctrl>-<Alt>-<Del>). I end up having to do a hard reset on the computer.

I have Windows 7 Professional running on an AMD Phenom II x4 980 Black Edition with 16GB of Corsair Vengeance RAM, an XFX Radeon HD 7970 Black Edition (3GB vRAM), 256GB Crucial SSD (plus two hard drives), Creative X-Fi on the motherboard (ASUS Crosshair IV Formula).

Since I cannot bring up the task manager, I cannot set the affinity (I know the system default is to run all software on all 4 cores), and I cannot see if the game is running or not.

Watching to see if GOG replies.

I believe you've suffered the same issue as me and regardless of whether this thread is several years old or not, I figured I'd bring my solution to your attention.
http://www.gog.com/forum/amerzone_the_explorer_s_legacy/ctd_on_win7_64bit_solution/post1
Hope it helps! :)