Abstract Purpose To develop a precision tissue sampling technique that uses computed tomography (CT)–based radiomic tumour habitats for ultrasound (US)-guided targeted biopsies that can be integrated in the clinical workflow of patients with high-grade serous ovarian cancer (HGSOC). Methods Six patients with suspected HGSOC scheduled for US-guided biopsy before starting neoadjuvant chemotherapy were included in this prospective study from September 2019 to February 2020. The tumour segmentation was performed manually on the pre-biopsy contrast-enhanced CT scan. Spatial radiomic maps were used to identify tumour areas with similar or distinct radiomic patterns, and tumour habitats were identified using the Gaussian mixture modelling. CT images with superimposed habitat maps were co-registered with US images by means of a landmark-based rigid registration method for US-guided targeted biopsies. The dice similarity coefficient (DSC) was used to assess the tumour-specific CT/US fusion accuracy. Results We successfully co-registered CT-based radiomic tumour habitats with US images in all patients. The median time between CT scan and biopsy was 21 days (range 7–30 days). The median DSC for tumour-specific CT/US fusion accuracy was 0.53 (range 0.79 to 0.37). The CT/US fusion accuracy was high for the larger pelvic tumours (DSC: 0.76–0.79) while it was lower for the smaller omental metastases (DSC: 0.37–0.53). Conclusion We developed a precision tissue sampling technique that uses radiomic habitats to guide in vivo biopsies using CT/US fusion and that can be seamlessly integrated in the clinical routine for patients with HGSOC. Key Points • We developed a prevision tissue sampling technique that co-registers CT-based radiomics–based tumour habitats with US images. • The CT/US fusion accuracy was high for the larger pelvic tumours (DSC: 0.76–0.79) while it was lower for the smaller omental metastases (DSC: 0.37–0.53).