BizTalk360 heavily depends on the Microsoft.BizTalk.ExplorerOM DLL that comes with Microsoft BizTalk Server. One of the restrictions of the component is that it does not support 64-bit.
IIS 7.0
IIS 7.0 is much more granular than IIS 6.0. Therefore, you can setup 32-bit mode at the Application Pool level rather than on server level, allowing to run both 32-bit and 64-bit application on the same server.
Here's how you can set this up from the IIS 7 Manager:
Right click on the Application Pool and select "Advanced Settings…" or select the same from the Actions pane after selecting the Application pool
Change the "Enable 32-bit Applications" to True (if you want the application pool to spawn in a 32-bit mode)
Click OK to save the changes
IIS 6.0
Note:
On systems with IIS 6, the Enable32bitAppOnWin64 property is a global property that affects all websites and applications on an IIS server. Make sure you do not have any other 64-bit applications running on the same server or plan to run BizTalk360 in a different server and point to the environment remotely.
ASP.NET 2.0, 32-bit version
To run the 32-bit version of ASP.NET 2.0, follow these steps:
Click Start > Run. Type cmd, and then click OK
Type the following command to enable the 32-bit mode:
cscript %SYSTEMDRIVE%\inetpub\adminscripts\adsutil.vbs SET W3SVC/AppPools/Enable32bitAppOnWin64 1
Type the following command to install the version of ASP.NET 2.0 (32-bit) and to install the script maps at the IIS root and under:
%SYSTEMROOT%\Microsoft.NET\Framework\v2.0.50727\aspnet_regiis.exe -i
Make sure that the status of ASP.NET version 2.0.50727 (32-bit) is set to Allowed in the Web service extension list in Internet Information Services Manager