Over the past 2 decades, there have been incredible advances in the pharmacotherapeutic options for the treatment of patients with moderately to severely active Crohn's disease. Despite the leaps and strides in safety, efficacy, and mechanistic specificity of treatment targets, a significant portion (up to approximately 20-50%) of patients have refractory Crohn's disease +/- concomitant rheumatologic disease/extraintestinal manifestations for which existing biologic and small molecule therapies are ineffective. In this review, we will explore the available evidence for the use of dual advanced therapies (combination of biologic and/or small molecule therapies) and novel pharmacotherapies in phase 2 to 3 clinical trials.