Management of pulmonary nodules in terms of diagnosis and intraoperative localization can be challenging, especially in the minimal invasive video-assisted thoracoscopic surgery (VATS) approach, and may be even more difficult with single port VATS with limited access. The ability to localize small lesions intraoperatively is particularly important for excisional biopsy for diagnostic frozen section, as well as to guide sublobar resection. Some of the common techniques to aid localization include preoperative percutaneous hookwire localization, colour dye or radio-dye labelling injection of the nodule or adjacent site to allowing visualization or detection by radioactive counter intraoperatively. The use of hybrid operating room (OR) for intraoperative localization of lung nodules was first reported in 2013, and was called image guided VATS (iVATS). Subsequently, we have expanded the iVATS application for single port VATS major lung resection of small or ground-glass opacity lesions. By performing an on-table cone-beam CT scan, real-time and accurate assessment of the pulmonary lesion can be made, which can aid the localization process. Other types of physical or colour marker that can be deployed percutaneously in the hybrid OR immediate before surgery can enhance haptic feedback and sensitivity of digital palpation, as well as provide a radiopaque nidus for radiological confirmation. In the past decade, the electromagnetic navigation bronchoscopy (ENB) technology had developed into a useful adjunct technology for the localization of peripheral lung nodules by injection of marking agent or deployment of fiducial to the lesion through the endobronchial route causing much lower marking agent diffusion and artefacts. Recently, the combination of hybrid OR and ENB for lung nodule localization and marking has further increased the accuracy and applicability of the technology. The article will be exploring the latest development of the above approaches to lung nodule localization, and discuss some of the techniques’ advantages and flaws.