From 1999 to 2004, Serge Honegger worked as an assistant director for the Zurich Opera House and accompanied Robert Wilson's "Ring" cycle, among others. As dramaturge, he supervised Heinz Spoerli's production of Jean-Philippe Rameau's "Les indes galantes" with the Zurich Ballet. This was followed by Vladimir Malakhov's "Cinderella" at the Staatsoper unter den Linden Berlin. As dramaturge and assistant director to Rebecca Horn, he realised "Elektra" for the International May Festival at the Hessisches Staatstheater Wiesbaden in 2010. Until 2015, he was head dramaturge at the St.Gallen Theatre for musical theatre productions.

Among the dance and theatre artists with whom Serge Honegger has worked are Özkan Ayik, Liliana Cavani, David Dawson, Charlotte Edmonds, Jürgen Flimm, Marco Goecke, Yossi Berg & Oded Graf, Claus Guth, Daniel Hay-Gordon, Jens-Daniel Herzog, Linda Kapetanea & Jozef Frucek, Laurent Hilaire, Andrey Kaydanovskiy, Konstantin Keykhel, Marcel Leemann, Sol León and Paul Lightfoot, Jonathan Lunn, Vladimir Malakhov, Yuki Mori, Marion Motin, Nicolas Paul, Angelin Preljocaj, Alexei Ratmansky, Marco Santi, Liam Scarlett, Johannes Schmid, Heinz Spoerli, Stephan Thoss, Beate Vollack and Robert Wilson.

Since 2004, he has worked as a dramaturge and artistic director on productions in the field of music theatre (dance productions, operas, oratorios, performances and staged concerts). An important focus of his work is on interdisciplinary and participatory forms of theatre. Performances under his artistic direction have been shown at Theaterspektakel Zürich ("REQUIEMreloaded"), Hessisches Staatstheater Wiesbaden ("Winterreise") and Theater St.Gallen ("Das Herz bebt im Stillen"). In 2020/2021, "I am not alone", a live soundscape on the ancient Via Egnatia route, was created in collaboration with Manuela Casari and Claudio Mascolo. It involved 16 museums and 15 writers from all language regions of Switzerland. In 2022, he realised "Street Ballads II" in Bulgaria, an interdisciplinary artistic exchange project between artists from Switzerland and Bulgaria. In September 2023, the live soundscape "Street Ballads III" premiered at the Kunsthaus Zürich with an 18-member performance ensemble and contributions from Ukrainian writers. In February 2024, the digital comic "Sakuntalas Ring", curated by him and Martina Borsche, was published and will be performed as a participatory dance piece at the Bayerische Staatsoper in September 2024.