A compact, portable, label-free, and ultra-sensitive sensor is proposed to detect cancerous cells based on Multi-Core Fiber (MCF) comprising of seven cores arranged in a hexagonal shape spliced with Single-Mode Fiber (SMF). Here, cytosensing based on fiber optic Localized Surface Plasmon Resonance (LSPR) is used for the efficient detection of different types of cancer cells. The proposed sensor structure is etched in a controlled manner to increase the evanescent wave (EWs) and coupling of modes between the cores of MCF. The etched MCF based LSPR probe has high refractive index sensitivity (RIS). To further increase the sensitivity, the sensor structure is immobilized with different nanomaterials (NMs) such as optimized size of gold nanoparticles (AuNPs), graphene oxide (GO), and copper oxide nanoflowers (CuO-NFs). AuNPs increase the sensitivity using LSPR, whereas, GO and CuO-NFs helps to increase the biocompatibility of sensor. The developed probe is further coated with 2-deoxy-D-glucose (2-DG) over NMs that are specific for the detection of cancer cells. In this work, various cancerous cell lines i.e. HepG2, Hepa 1–6, MCF-7, A549, and normal cell lines i.e. NCF and LO2 are detected using the developed sensing probe. Various analysis of proposed sensor such as selectivity, reusability, anti-interference ability, and involvement of GLUT receptor in detection has also been performed. The proposed etched sensor is ultra-sensitive for detection of HepG2, Hepa1 6, A549, MCF-7, LO2, and NCF cell lines with a limit of detection (LoD) of 3, 2, 2, 2, 4, 10 cells/mL, respectively in the linear range of 1 × 102–1 × 106 cells/mL.