Whilst playing with Pencey Prep he became friends with Gerard Way and the other My Chemical Romance members, and became a fan of their original demo and helped them get their first shows.

My Chemical Romance's fourth and final studio album Danger Days: The True Lives of the Fabulous Killjoys was released on November 22, 2010.

Iero fronted the hardcore punk quintet Leathermouth, who released their debut album XO in January 2009 on Epitaph Records.

He later posted an anti-Xmas track he recorded as a joke in 15 minutes and followed that up with a cover of the song 'Be My Baby', originally made famous by the Ronettes.

[7] In early 2013 Iero and James Dewees announced that they were working on a new project, a digital hardcore act called Death Spells.

Starting a week before the Mindless Self Indulgence tour Death Spells posted a short demo of a new song each night at midnight, culminating this with their first full single Where Are My Fucking Pills?

Throughout the rest of 2013 he started playing a couple of songs live at events, posted a demo of "joyriding", and recorded a full-length album.

[13] In June 2014 he announced his signing to Staples Records and his debut album called Stomachaches due out August 25, under the moniker frnkiero andthe cellabration.

The band announced headline dates for 2015 in Mexico, the US, and Europe and played the Reading and Leeds festivals of that year.

On May 22, 2016 they officially announced recording a new album and an Australian tour, with a name change to the band, to be then known as Frank Iero and the Patience.

The band performed at Shadow of the City with the 1975 in New Jersey and played both Riot Fest dates (Denver and Chicago) in September 2016.

[17] On October 31, 2019, My Chemical Romance announced they would be reuniting with a date in Los Angeles on December 20 and a new merchandise line.

Iero, along with the Fender Custom Shop co-developed a guitar known as the "Frank"enstein Fender Jaguar, which has now become a staple of Iero's collection, Based upon the body of a long scale Jaguar crafted by Masterbuilder Dennis Galuszka, combined with the neck of 'offset connoisseur' Mike 'Puisheen' Adams' vintage Jazzmaster which was discovered in a waterlogged basement.

Iero had the guitar finished in a black relic with matching headstock, tortoiseshell pick guard, rosewood fingerboard and pearloid block inlays.

Example 1 also features custom Scorpion inlaid speed dial knobs crafted by Iero's friend James Bowman.

[28] When playing with ex-My Chemical Romance keyboardist James Dewees' band Reggie and the Full Effect, replacing late Slipknot bassist Paul Gray on bass, he played a black Fender Precision Bass through an Ampeg 8x10 amplifier previously owned by MCR bassist Mikey Way, the latter of which he sold amongst many other items in his vast collection in 2023.

When Epiphone reached out to Iero about supplying guitars for their upcoming tours and the idea of a signature was thrown in the air, Iero swooped on it to create a guitar that retained the Les Paul tone and feel whilst shedding the weight of a Les Paul to reduce fatigue and back strain.

[29] On September 7, 2010, Iero announced on the My Chemical Romance official website that he and his wife Jamia had become parents of twin girls.

"[33][34] In response to Donald Trump winning the United States presidential election of 2016 Iero tweeted, "I feel sad and ashamed.

'"[35] In 2019, Iero shared in an interview with Hysteria magazine that he experiences synesthesia, adding that “It’s very hard to explain because I don’t know why I feel that way or why I see it that way.