The recent improvements in diagnosis enabled by advances in liquid biopsy and oncological imaging significantly better cancer care. Both these complementary approaches, which are used for early tumor detection, characterization, and monitoring, can benefit from applying techniques based on surface-enhanced Raman scattering (SERS). With a detection sensitivity at the single-molecule level, SERS spectroscopy is widely used in cell and molecular biology, and its capability for the in vitro detection of several types of cancer biomarkers is well established. In the last few years, several intriguing SERS applications have emerged, including in vivo imaging for tumor targeting and the monitoring of drug release. In this paper, selected recent developments and trends in SERS applications in the field of liquid biopsy and tumor imaging are critically reviewed, with a special emphasis on results that demonstrate the clinical utility of SERS.