Yes.
Just make sure the path to program you enter is a correct relative path. relative to the installation folder of Multi Commander.
Eg
MultiCommander is installed in E:\MCPortable\
You got Notepad++ in E:\Bin\Notepad++\Notepad++.exe
Then call notepad++.exe using a relative path like
"..\Bin\Notepad++\Notepad++.exe"
For example if using "custom commands" for the button and you want the program to get the file in focus as a parameter
MC.Run CMD="..\Bin\Notepad++\notepad++.exe" ARG="${focusfilepath}"