Bronchoscopic biopsy results for indeterminate pulmonary nodules remain suboptimal. Electromagnetic navigation bronchoscopy (ENB) coupled with cone beam computed tomography (CBCT) for confirmation has the potential to improve diagnostic yield. We present our experience using this multimodal approach to biopsy 17 indeterminate nodules in 14 consecutive patients from April to August 2021. Demographic information, nodule characteristics, and biopsy results were recorded. Procedures were performed in a hybrid operating room equipped with a Siemens Artis Q bi-plane CBCT (Siemens, Munich, Germany). After ENB using the superDimension version 7.1 (Medtronic, Plymouth, MN, USA) to target the lesion, radial endobronchial ultrasound was used as secondary confirmation. Next, transbronchial needle aspiration was performed prior to CBCT to evaluate placement of the biopsy tool in the lesion. The average nodule size was 21.7+/−15 mm with 59% (10/17) < 2 cm in all dimensions and 35% (6/17) showing a radiographic bronchus sign. The diagnostic yield of CBCT-guided ENB was 76% (13/17). No immediate periprocedural or postprocedural complications were identified. Our experience with CBCT-guided ENB further supports the comparable efficacy and safety of this procedure compared to other mature biopsy modalities. Studies designed to optimize the lung nodule biopsy process and to determine the contributions from different procedural aspects are warranted.