After Toxic Orb activates Quick Feet, Mightyena reaches a blistering Speed stat of 393, enough to outspeed the entire unboosted UU metagame bar Electrode while keeping the ability to switch between moves. This would make Mightyena the quintessential revenge killer if it weren't for Mightyena's lack of offensive power. With a status condition inflicted, Facade becomes Mightyena's strongest attack, which is highly disappointing as it doesn't even get STAB. Fortunately, Mightyena is still powerful enough to KO many frail UU threats with Stealth Rock support being necessary for several of these KOs. The main idea when using Mightyena mid-game is to bring it in on a Pokemon it can revenge kill with Sucker Punch, such as Rotom, Mismagius, and Alakazam, and eliminate them. After this, Mightyena's Toxic Orb will activate, firing its Speed stat up to the heavens and beyond.
Crunch is used primarily so that Mightyena doesn't have to rely on the oftentimes unreliable Sucker Punch for STAB, although Mightyena's movepool is so poor there isn't really any other option anyway. The last slot comes down to personal preference. As Mightyena's Attack stat is quite lackluster, Howl can be used to raise it, which will allow Mightyena to 2HKO bulkier threats, such as Venusaur and Uxie. Taunt can be used in its place to shut down walls that will inevitably switch into Mightyena, like Registeel, and it can also prevent specific threats from setting up on Mightyena as it switches out, such as Rhyperior and Aggron.
Some other options that can be used in the last slot include Protect, Super Fang, and Yawn. Protect allows Mightyena to activate its Toxic Orb scot-free while scouting your opponent's switch-in; however, Howl and Taunt are hard to replace, and so are Mightyena's attacking moves. Super Fang strips bulky walls, such as Weezing and Rhyperior, of half their health, allowing Mightyena's teammates to eliminate them more easily. Yawn can cause switches to help Mightyena activate its Toxic Orb and may even put something to sleep heaven forbid.
Toxic Orb is the chosen item for this set as it activates Quick Feet with no drawbacks other than inflicting poison on Mightyena. Flame Orb cannot be used as, unlike the ability Guts, Quick Feet will not cancel out the Attack drop caused by the burn condition. Finally, Mightyena can switch into Thunder Wave safely, as Quick Feet will still activate and Mightyena will receive the Speed boost as normal. Unfortunately, there is a chance that full paralysis will occur, so don't play too loosely with Mightyena in that regard.
In order for Mightyena to be successful, it needs some heavy duty team support. U-turn users are amazing partners, particularly slow users such as Uxie, as they can get Mightyena in safely and activate its Toxic Orb without the need for Protect or utilizing the Sucker Punch strategy described above. Mightyena is easily walled by Registeel, Milotic, Rhyperior, and Weezing, so including a powerful special sweeper on your team will allow Mightyena to bypass these threats. Life Orb Milotic and Physical Sweeper Venusaur make great teammates as they can handle the aforementioned Pokemon quite nicely, and they appreciate Mightyena's ability to pick off faster sweepers, such as Swellow, Sceptile, and Rotom.