This question has recently come up in discussion and other circles:
Can the server component of MapGuide Enterprise be installed and run on a 64-bit version of the Windows operating system, while the web server extensions are installed and run on a 32-bit version of the Windows operating system?
Rationale given for these types of scenarios might include where a custom application was developed for 32-bit only, but it is desirable to run the server on a 64-bit OS for performance or other considerations.
At this point, the answer is 'no'. The web extensions and the server component of MapGuide Enterprise can communicate in either 32-bit or 64-bit, but not both at the same time. Therefore, mixing 32-bit and 64-bit is unsupported.
Zac Travis