In OctoPrint's Terminal tab:
The printer should attempt to HOME all motors X/Y/Z. Presumably, you expect the assembly to move to the left/rear of the printer.
Set the positioning to absolute mode. Any commands after this will be absolute coordinates.
G0 X100 Y100
You're hoping that the assembly moves right by 100mm and forward by 100mm.
If all this produces the expected results, then your OctoPrint and its profile is happy. (It's entirely possible that you didn't home the motors before sending the job, btw.)
I don't know Simplify 3D but I'd guess that it's set correctly.
Take 2: You didn't mention whether or not that both of these are true 1) you have a dual extruder printer and 2) you're attempting to print from the 2nd extruder. If so and your extruder offset is wrong then it might behave like this.