Where spiders might be up against it? (2,1,6)
I believe the answer is:
in a corner
I believe this is a double definition.
'where spiders might be' is the first definition.
(spiders may be chased into a corner)
'up against it?' is the second definition.
(both can mean in a difficult situation)
(Other definitions for in a corner that I've seen before include "unable to escape" , "Like rook initially" .)