[3] She discovered comics at the age of four, when her mother began bringing her I. W. Publications titles she bought at Woolworth.

[3] Early influences from the comic book world included Stan Lee, Jack Kirby, Roy Thomas, Robert Kanigher, and Len Wein; Isabella also cited being influenced by William Shakespeare, Harlan Ellison, Ed McBain, Neil Simon, Mel Brooks, Lester Dent, Dave Barry, Max Allan Collins, Don Pendleton, and Studs Terkel.

The Living Colossus in Astonishing Tales, Luke Cage in Hero for Hire and Power Man, Tigra in Marvel Chillers, Daredevil,[7] and Captain America.

[8] While writing the "Iron Fist" feature in Marvel Premiere, she co-created the supporting character Misty Knight with artist Arvell Jones.

[10][11] During her mid-1970s run on Ghost Rider, Isabella wrote a two-year story arc in which Johnny Blaze occasionally encountered an unnamed character referred to as "the Friend" who protected him from Satan, the source of his supernatural powers and identity as Ghost Rider.

Had I remained on Ghost Rider, which was my intent at the time, the title's religious elements would have faded into the background.

He had some of the art redrawn and a lot of the copy rewritten to change the ending of a story two years in the making.

[15] Isabella worked as a writer and story editor for DC Comics,[6] and is known for creating Black Lightning,[16] and writing both the character's short-lived 1970s and 1990s series.

[17] After reaching an agreement with DC,[18] Isabella returned to the character in 2017 with the publication of the Black Lightning: Cold Dead Hands limited series.

The ongoing book became one of Comico's best-selling series, selling upwards of 70,000 copies of each issue at its peak.

[28] The pair also wrote the novels Captain America: Liberty's Torch (1998)[29] and Star Trek: The Case Of The Colonist's Corpse (2003).