Upon entering a biological environment, the surface of nanoparticles (NPs) is rapidly coated by various biomolecules (typically proteins), herein referred to as the biological corona fingerprint, representing a rich source of biological information that can guide the development of diagnosis, prognosis, and therapeutics for diverse disorders. Although the number of studies has been increasing and considerable technological success has been achieved over the past few years, the main obstacles in this field stem from the complexities and heterogeneity of disease biology due to an incomplete understanding of nano-bio interactions and the challenges regarding the chemistry, manufacturing, and controls required for clinical translation. This minireview highlights the progress, challenges, and opportunities in nano-biological corona fingerprinting for diagnosis, prognosis, and therapeutics, and offers suggestions for more effective nano-therapeutics by capitalizing on our growing understanding of tumor biology and nano-bio interactions. Encouragingly, the current understanding of biological fingerprints could favor the development of optimal delivery systems that use the NP-biological interaction rationale and computational analyses to guide more desirable nanomedicine designs and delivery strategies.