The Nernst effect, a transverse thermoelectric phenomenon, has attracted significant attention for its potential in energy conversion, thermoelectrics and spintronics. However, achieving high performance and versatility at low temperatures remains elusive. Here we demonstrate a large and electrically tunable Nernst effect by combining the electrical properties of graphene with the semiconducting characteristics of indium selenide in a field-effect geometry. Our results establish a new platform for exploring and manipulating this thermoelectric effect, showcasing the first electrical tunability with an on/off ratio of 103. Moreover, photovoltage measurements reveal a stronger photo-Nernst signal in the graphene/indium selenide heterostructure compared with individual components. Remarkably, we observe a record-high Nernst coefficient of 66.4 μV K−1 T−1 at ultralow temperatures and low magnetic fields, an important step towards applications in quantum information and low-temperature emergent phenomena.