Modification of interface between metal sulfide phases is a very promising strategy for designing advanced catalytic materials. Herein, a novel bimetallic sulfide of Molybdenum disulfide covered Samarium sulfide (α-Sm 2 S 3 /MoS 2 ) with van der Waals heterogeneous nanostructure was produced for the first time via a simple one-step hydrothermal method. The XRD, FESEM, HRTEM, EDX and XPS results substantiate the successful formation of composite and the modified α-Sm 2 S 3 /MoS 2 potentially exploited as an electrode for determination of antineoplastic drug 5-Fluorouracil (5-FU). Owing to the rich active sites, synergistic function from α-Sm 2 S 3 and MoS 2 and rapid electron transportation, α-Sm 2 S 3 /MoS 2 sensor platform exhibits considerable electrochemical sensing performance with a linear range from 0.1-1166 μM, and the low detection limit (0.015 μM at S/N = 3). The α-Sm 2 S 3 /MoS 2 sensing performance is highly selective, stable, and reproducible (with relative standard deviations of 4.28%). The excellent practical utility of the α-Sm 2 S 3 /MoS 2 sensor comprehends from the quantification of 5-FU in serum and urine samples with acceptable recoveries. Hence, this particular report, open up a paves to design efficient electrode materials by a simple synthesis method for electrochemical application.