He started professional work in the field of comic book drawing for Italian publishers Comic Art and later Sergio Bonelli Editore, where he mostly worked on the Nick Raider series. His work was also occasionally featured in the Métal Hurlant and Comic Art magazines. At age 27, he moved to France to work on storyboarding production and directed several animated TV series and feature films.
He moved back to his native Marche in 1995, when he founded the Rainbow animation studio, initially providing services for other studios, but eventually producing its first original product, the Tommy and Oscar animated CD (1996) and later TV series (1999). His most successful creation, Winx Club, debuted in 2004, and became a worldwide success. It is now broadcast in over 130 countries, across Europe, the United States and most of Asia. Aside from its headquarters near Loreto, Marche, Rainbow now has branch offices in Rome and Singapore.
Other Rainbow creations include Prezzy (inspired by the Italian Gardalandtheme parkmascot) and Monster Allergy (also a successful Disneycomic book), as well as co-production of Huntik. Iginio and Rainbow have created "Rainbow Magic Land", which opened in Spring 2011, including a full-sized "Alfea" school (as seen in Winx Club). Huntik: Secrets & Seekers is one of Straffi's most famous and well-known series, and has been broadcast in many countries worldwide. Most recently he directed and produced Gladiators of Rome, which opened in Italy, October 2012. It received instant success, with some mixed reviews, and was later released across Europe and the Americas.