可能です。 64BitTwoArch.issサンプル（特にIs64BitInstallModeブール値）を見てください。
; -- 64BitTwoArch.iss --
; Demonstrates how to install a program built for two different
; architectures (x86 and x64) using a single installer.
; SEE THE DOCUMENTATION FOR DETAILS ON CREATING .ISS SCRIPT FILES!
[Setup]
AppName=My Program
AppVersion=1.5
DefaultDirName={pf}\My Program
DefaultGroupName=My Program
UninstallDisplayIcon={app}\MyProg.exe
Compression=lzma2
SolidCompression=yes
OutputDir=userdocs:Inno Setup Examples Output
; "ArchitecturesInstallIn64BitMode=x64" requests that the install be
; done in "64-bit mode" on x64, meaning it should use the native
; 64-bit Program Files directory and the 64-bit view of the registry.
; On all other architectures it will install in "32-bit mode".
ArchitecturesInstallIn64BitMode=x64
; Note: We don't set ProcessorsAllowed because we want this
; installation to run on all architectures (including Itanium,
; since it's capable of running 32-bit code too).
[Files]
; Install MyProg-x64.exe if running in 64-bit mode (x64; see above),
; MyProg.exe otherwise.
Source: "MyProg-x64.exe"; DestDir: "{app}"; DestName: "MyProg.exe"; Check: Is64BitInstallMode
Source: "MyProg.exe"; DestDir: "{app}"; Check: not Is64BitInstallMode
Source: "MyProg.chm"; DestDir: "{app}"
Source: "Readme.txt"; DestDir: "{app}"; Flags: isreadme
[Icons]
Name: "{group}\My Program"; Filename: "{app}\MyProg.exe"