Simple, fast, selective, and reliable detection of human epidermal growth factor receptor 2 (HER2) is of utmost importance in the early diagnosis of breast cancer to prevent its high prevalence and mortality. Molecularly imprinted polymers (MIPs), also known as artificial antibodies, have recently been used as a specific tool in cancer diagnosis and therapy. In this study, a miniaturized surface plasmon resonance (SPR)-based sensor was developed using epitope-mediated HER2-nanoMIPs. The nanoMIP receptors were characterized using dynamic light scattering (DLS), zeta potential, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and fluorescent microscopy. The average size of the nanoMIPs was determined to be 67.5 ± 12.5 nm. The proposed novel SPR sensor provided superior selectivity to HER2 with a detection limit (LOD) of 11.6 pg mL−1in human serum. The high specificity of the sensor was confirmed by cross-reactivity studies using P53, human serum albumin (HSA), transferrin, and glucose. The sensor preparation steps were successfully characterized by employing cyclic and square wave voltammetry. The nanoMIP–SPR sensor demonstrates great potential for use in the early diagnosis of breast cancer as a robust tool with high sensitivity, selectivity, and specificity.