If you've played the original card game upon which this video game version is meticulously based, you'll have no trouble adapting - though it's dificult to see the entire playfield smashed onto the DS' touch screen (the other screen is used for close-ups of individual cards), this is a down-to-the-stitching recreation. There are even robust multiplayer features ranging from head to head action, full online tournaments, and cross-platform gaming with those PSP guys.
If you aren't familiar with the source, get ready for a very steep learning curve. There are character cards, which do the actual "fighting" each round based upon their attack and defense ratings. There are location and equipment cards that give various bonuses (for instance, giving the Thing a gun enables him to attack from the back row instead of just the front). And there are "plot twist" cards, that blow huge holes in any detailed strategy. For example, Spider Senses will boost certain character cards' defense by three points for one round.
The thing that makes it complex is that nearly every time a card is placed or used (two different actions, for the record), there's the option for the other player to counter with another card, and many have multiple obscure abilities. That's not to mention the character cards' abilities to augment and block one another, or team affiliation, evasion, reserves, concealment... the list goes on. Luckily, there are massive tutorials, but you'll need to watch each several times to fully absorb it all. In the meantime, you'll probably take quite a few lumps.