I'm thinking this has to be one of the easiest investigator weaknesses to deal with in the entire game, short of the ones you can afford to outright ignore sometimes. Most of the cards that help Trish deal with this weakness are cards she would have strongly considered running anyway.

Narrow Escape is already fantastic for Trish, this weakness practically makes it a cornerstone.

Obfuscation also helps with this and slides right into a completely uncontested slot (arcane). Since it's Fast, she can hold onto it until she needs it.

Cryptographic Cipher helps as well. Despite making the resulting investigate slightly tougher, at any 1 or 2 shroud location it's hardly noticeable and it lets her grab a clue AND discard her weakness without spending a single action. If it's sitting in her hand she could always Sleight of Hand it out as well...

Shortcut helps her position herself on top of a clue if she draws into this weakness at a location with 0 clues.

...and if there are no clues around you could always stoop to the level of more mortal investigators and simply spend an action to evade it and poof, it's gone.

Pretty cool. Trish seems extremely hard to slow down.

An enemy signature weakness, designed to annoy Trish. Looking at the two elements, the effect and the discard condition, we get:

The effect: There are three ways to deal with this weakness, the mug's way, Trish's way, and Trish's other way. The mug's way is to fight them; that is likely to be 2, maybe 3 actions, although another investigator can always do the fighting for Trish. Trish's way is to evade them. As a , Trish has a lot of evade options. The entries above give some good suggestions, and Slip Away, Slip Away (2), Stealth, and Manual Dexterity (2) can help with the test. Trish's other way mostly involves boosting investigation checks and using Obfuscation to ignore the AoO (or just eat the damage; Trish has 8 health) and relying on Trish's special ability to evade them. The real secret of the Shadow Agents is: why are they hunters? If they get discarded, they aren't going to hunt, and there aren't too many cards that move an investigator without bringing the enemy with them.

The discard condition: Evade them or kill them.

All in all, this is a below average signature weakness, like most enemy weaknesses.

Fastest ways to deal with this (assuming you don't want to test versus 5 or spend ammo):

1. Decoy
2. Pendant of the Queen, though it's much more likely for you to find this enemy before the three segments.
3. Let a friend engage it, then simply discover a clue at the same location.
4. If your deck has Obfuscation you just investigate through the attack and wave goodbye.

Edit: I thought it was an extremely mild weakness at first glance (well I still believe so), there's just one situation where it is quite annoying: when you draw it in upkeep in a location with no clues. Then you have to actually overcommit to an evasion or move with the agents. So just try to make sure to anticipate this.