Advances in nanotechnology have vastly expanded the library of nanomaterials with diverse chemical compositions, structures, and functions. Among these, calcium carbonate nanoparticles (CaNPs) are particularly promising for in vivo biomedical applications due to their excellent biocompatibility and unique pH-responsive degradability, which is ideal for targeted drug delivery in acidic tumor microenvironments. However, the practical translation of CaNPs is hindered by inherent challenges, such as colloidal instability and aggregation. This Perspective provides a critical analysis of recent advances in the synthesis, functionalization, and biomedical applications of CaNPs, with a focus on their role as platforms for therapeutic delivery. The review systematically summarizes synthesis methods and examines the efficacy of CaNPs as carriers for chemotherapeutic agents, nucleic acids, proteins, and antigens. Furthermore, it explores their emerging potential in tissue engineering. A key finding of this analysis is that while surface modification strategies can significantly enhance the stability and targeting ability of CaNPs, achieving long-term colloidal stability in vivo remains a primary challenge. The review concludes that CaNPs hold substantial promise for revolutionizing anticancer therapy and regenerative medicine. However, their clinical adoption is contingent upon overcoming limitations in large-scale, reproducible synthesis and a comprehensive understanding of their long-term biocompatibility. By synthesizing current knowledge and identifying future directions, this review addresses a critical gap and aims to accelerate the development of next-generation CaNPs-based biomedical platforms.