Glamorgan face an uphill battle against Middlesex after being bowled out for 171 in their first innings.
David Lloyd top scored with 67, however Tom Helm (5-53) and Toby Roland-Jones (4/45) put the visitors on top, before Sam Robson cemented Middlesex' position with 73* as they reached 189/5 in their second innings - an overall lead of 402.
"A very difficult day, they hit their lengths more regularly than we did, then we started well with the ball in the second dig but it's always tough when you're chasing the game," said Lloyd.
"It's a wicket where you have to be positive and get forward because it's starting to go more up and down- it's about looking to score rather than sit there and wait for things to happen.
"We've showed in previous games that we can battle draws out so you never know, we'll have to try to bat the rest of the game and we can do it if we get our mindsets right."