Many things need to be set properly for this to work and that follows below. Sorry, I tried to make this as short as possible.
First off, the game needs to be run once outside of MO via the games launcher to set paths in the Windows registry. I believe the “esl” files are not supported at this time in Smash or I have missed an update along the way.
For the Mator Smash to work with MO, MO2 needs to be installed in the “Portable” mode.
To change to portable mode, click the far-left icon. You will be told that MO will restart, click yes. In the next window that opens select “Portable Mode”. The window will close, and the game selection window will open with all installed recognized games along with the path to the game executable. Click on Fallout 4. Click through the dialogs about the tutorials as needed. MO2 will open the main window.
Click on the settings button, wrench and screwdriver icon, and click on the “Paths” tab. Make sure the “Base Directory” points to the MO2 install directory, it should by default. The rest of the “Path” directories should look like “%BASE_DIR%/Directory-Name”. If your ‘Mods” and “Download” locations need to be changed to another hard drive you can change it here. Leave the rest of the paths as default. Click Ok to store any changes.
Add Mator Smash to MO2. Click the executable drop down next to the run button and select “Edit”. The “Modify Executables” dialog will open. In the title box give the executable a name. In the “Binary” section click the button and browse to the Mator Smash executable and select it. Click “Open” to return the Modify Executables window. Click “ADD” to add the program to the executable list.
Run Smash by selecting it from the Executables dropdown and press the run button.
The Game selection window will open with all installed games it supports. There should be a selection for fallout 4, click on it and the “OK” button will become active, click OK to continue. The plugin selection window open. At this time only select “Fallout4.esm” and click OK. The main Smash window will open. Click the options button and the settings window will open. Click on the “Integrations” tab if it did not open there. The program should have detected the MO2 install and the “I’m using Mod Organizer” should be checked along with the paths to the MO2 folder along with the mods folder. If the dialog is empty, click the Detect Integrations button or manually provide the paths to the appropriate locations. Click on the “Patching” tab and make sure that it points to the mods folder from the Integrations Tab. Click OK to store the settings. You will be returned to the main window.
At this point Smash should now work from MO2.
Extra info: You can skip the game selection by entering "-profile FO4" in the arguments box in the Mator Smash executable section, don't include the quotes.
I hope this helps.