Two-dimensional (2D) materials-based fiber-optic surface plasmon resonance (SPR) sensor is proposed to diagnose the different cancers at the wavelength of 1550 nm. In this work, five types of cancerous cell lines such as Jurkat, HeLa, PC12, MDA-MB-231, MCF7, and normal cell lines are considered for analysis. The power loss through proposed SPR sensor is maximum at a specific angle <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${\theta }_{\textit {SPR}}$ </tex-math></inline-formula> . Resonance angle <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${\theta }_{\textit {SPR}}$ </tex-math></inline-formula> shift to another angle for different cancerous cell lines. The angular shift and power loss of different cancerous cells are different from their normal cells due to the different refractive indices (RIs) of each cell. The proposed work is helpful in the detection of different types of cancer such as blood, cervical, Adrenal Glands and Breast Cancer by measuring the angular shift in peak power loss. For angular power loss calculations, transfer matrix method (TMM) is used. The sensor structure consists of fiber core, clad, metal layer, and 2D material layer. In 2D material, role of MoS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> and graphene are investigated on the performance of sensor. Further, three structures such as (i) probe 1: SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -perfluorinated (PF)-Ag (ii) probe 2: SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -PF-Ag-MoS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> , and (iii) probe 3: SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -PF-Ag-graphene are designed and investigated in detail. Calculated values of a figure of merit (FOM) for probe 2, probe 1, and probe 3 sensor structure are 6654.54 RIU <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−1</sup> , 4645.21 RIU <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−1</sup> , and 832.88 RIU <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−1</sup> , respectively. Sensitivity and limit of detection (LoD) are also calculated from power loss spectrum. Probe 2 provides maximum FOM in all and exhibits three times larger FOM than earlier reported cancer cell sensors. The calculated LoD in case of probe 2 for Jurkat, HeLa, PC12, MDA-MB-231, MCF7 are 0.4550 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−5</sup> , 0.4510 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−5</sup> , 0.4440 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−5</sup> , 0.4350 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−5</sup> and 0.430 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−5</sup> respectively with maximum sensitivity of 232.33 deg./RIU. Thus, LoD of the proposed sensor is quite low that makes it better than most of the recently reported SPR based fiber-optic sensors. The proposed fiber optic SPR sensor with high FOM and low LoD is a suitable candidate for the early diagnosis of different types of cancers.