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Strixhaven: School of Mages is a bottom-up enemy color faction set based on “instants and spells matter”. Creatively, the design of this set is Magic’s take on the magical school genre. Each one of the featured colleges represents one of Magic’s enemy color combinations, with their own character and mechanics. Cards associated with the different colleges feature separate watermarked insignias. This set contains 275 regular cards (105 commons, 80 uncommons, 69 rares, 21 mythic rares) and includes randomly inserted premium versions of all cards. The basic lands are numbered outside the main set and therefore don't appear in the draft boosters.

Alternate card frames have another card number than the original version. Borderless planeswalkers are numbered #276-279, borderless elder dragons are #280-284, and extended artwork cards are numbered #285-365. Basic lands are #366-375. The Buy-a-Box card is #376 and the Bundle promo is #377. The FNM-treatment cards from the Universal promo pack are numbered #378-382. There are no showcase cards in this set, as the Mystical Archive fills that position.

This set introduces the term mana value as a wording change for converted mana cost. Also, "shuffle your library" is shortened to shuffle, and "activate this ability only any time you could cast a sorcery" is shortened to "activate only as a sorcery."