<p>Despite carbon-based nanomaterials such as carbon nanotubes, graphene derivatives, carbon dots, nanodiamonds, and fullerenes have been extensively studied as drug delivery systems, there is still little clinical application. The structure–property–biological response framework presented in this review connects pharmacokinetics, intracellular trafficking, protein corona formation, and long-term biodistribution to dimensionality, size distribution, surface oxidation, and functionalization stability. Drug-loading capacities ranging from 50 to &gt; 600 mg g^− 1 and tumor-inhibition rates of 30–75% are revealed by quantitative benchmarking across studies, highlighting significant performance variability attributable to physicochemical heterogeneity. We identify translational bottlenecks, such as batch variability, chirality control, surface-modification instability, immune activation, and regulatory constraints, and critically analyze differences between in vitro cytotoxicity enhancement and in vivo therapeutic outcomes. This review identifies significant design principles required for clinically viable carbon nanocarriers by combining mechanistic and manufacturing viewpoints with recent developments in biodegradable and stimuli-responsive carbon systems (2020–2025).</p> Graphical Abstract <p></p>