In situ biomanufacturing is redefining personalized and regenerative medicine by enabling therapeutic materials to be formed directly at target sites within the body. This emerging paradigm integrates advances in biomaterials, minimally invasive surgical tools and robotic systems, and ultrasound-guided activation platforms to achieve precise, on-demand material deposition or crosslinking without the need for open surgical access. This Review outlines the clinical challenges and requirements motivating these technologies — minimally invasive access, deep-tissue targeting, spatiotemporal precision and real-time monitoring — and describes how next-generation biomaterials, including shear-thinning, photoreactive, thermoresponsive and acoustically responsive hydrogels, are being engineered to meet these demands. Progress in fabrication strategies, ranging from hand-held and robotic bioprinters to near-infrared light-activated and ultrasound-activated systems capable of noninvasive or deep-tissue biofabrication, is summarized. Key applications in tissue regeneration, wound repair, localized drug delivery and in vivo bioelectronics are highlighted to illustrate the translational potential of these approaches. Finally, the major steps required for clinical adoption are described, including the development of materials optimized for in vivo activation, standardized evaluation frameworks, regulatory considerations for energy-activated platforms, and integration into clinical workflows. Together, these advances point towards a future in which patient-specific therapeutic structures can be fabricated directly within living tissues.