Isaac Klausner started out in Hollywood as an assistant director, working in movies like Good Boy, Bad Boy (2007), The Twilight Saga: New Moon (2009) and Dear John (2010) early on in his career. Subsequently, Klausner ventured into production as an associate producer with the third film in the Twilight series, The Twilight Saga: Eclipse (2010).

He has since worked as an executive producer in the romantic drama The Fault in Our Stars (2014), the romantic mystery comedy-drama Paper Towns (2015), besides bankrolling the acclaimed romantic comedy-drama Love, Simon (2018) and First Man (2018).