Spy Combo's entire plan is to cast Balustrade Spy, mill their library (they run no basics aside from Land Grant fetches), then flashback Dread Return to reanimate Lotleth Giant for lethal damage — so every piece of interaction you have is live. Counterspell and Spellstutter Sprite are your most important cards; prioritize holding up two mana to counter Balustrade Spy or Dread Return, and Snuff Out can kill the Spy at instant speed for free in response to its triggered ability. Post-board, Extract a Confession lets you strip combo pieces preemptively with hand disruption, while Bojuka Bog and Relic of Progenitus give you graveyard hate — hold the Bog for after they've assembled their graveyard and activate Relic in response to a Dread Return flashback to completely invalidate their kill. Arms of Hadar and Unexpected Fangs do nothing in this matchup, as their creature suite exists to accelerate mana rather than win in combat.