A nanophotonic photodetector is proposed with a multi-heterojunction structure based on silicon–ITO (Indium Tin Oxide) slot waveguide covered with 2D (two-dimensional) graphene sheets. A heavily n-doped ITO layer covers the whole device and works as an electrode to reduce the light loss at the metal–graphene interfaces. Different waveguides are arranged to design a one-dimensional photonic crystal (1D PhC) and the slot is defined by creating a defect in it. The PhC provides strong confinement of light, increasing the light–matter interaction, and thus generating more electron–hole (e–h) pairs or charge carriers under light illumination. Moreover, the multiple heterojunctions enhance the e–h generation and help enhancing the transportation of charge carriers. As a result, high photocurrent, fast response across a large bandwidth, strong electron-photon interaction, and also enhancement of photocarrier multiplications can be achieved. The photodetector realizes a photoresponsivity beyond 0.6 A/W at around 1550 nm wavelength. From 0.5 V–2 V of the bias voltage, the difference between the photocurrent and the dark current for the device with the PhC is more than 5 times that for the device without the PhC. Moreover, a 25 Gbit/s non-return to zero optical transmission is measured at 10 km transmission. The proposed device has diverse applications such as telecommunications, optical computing, interconnects, laser radar, lab-on-chip for sensing, and on-chip quantum photonics.