Structured-light-based optical sensing has emerged as an effective approach for developing sensitive platforms in cancer-related detection. This work presents a fiber-optic biosensor using an Airy-Vortex beam (AVB) to improve the identification of cancer-related biomarkers. The sensor employs a multimode optical fiber with a decladded core region, thereby increasing evanescent-field interaction with the external environment and boosting light-matter interaction. The sensing mechanism relies on multimode interference (MMI), where variations in transmitted optical power correspond to variations in the analyte’s refractive index. Numerical simulations conducted using OptiBPM (version 13.1.3) at 1550 nm demonstrate a response of 888.7 dB/RIU, representing a 3.27-fold enhancement over conventional multimode fiber sensors.The AVB-based sensor differentiates HeLa, Jurkat, MCF7, and PC12 cell lines, indicating its capability to resolve cancer-associated cellular variations. The proposed sensor architecture is suitable for real-time optical biosensing and related biomedical diagnostic applications.