The development of sustainable, cost-efficient, and high-performance nanofluids is one of the current research topics within drilling applications. The inclusion of tailorable nanoparticles offers the possibility of formulating water-based fluids with enhanced properties, providing unprecedented opportunities in the energy, oil, gas, water, or infrastructure industries. In this work, the most recent and relevant findings related with the development of customizable nanofluids are discussed, focusing on those based on the incorporation of 2D (two-dimensional) nanoparticles and environmentally friendly precursors. The advantages and drawbacks of using 2D layered nanomaterials including but not limited to silicon nano-glass flakes, graphene, MoS2, disk-shaped Laponite nanoparticles, layered magnesium aluminum silicate nanoparticles, and nanolayered organo-montmorillonite are presented. The current formulation approaches are listed, as well as their physicochemical characterization: rheology, viscoelastic properties, and filtration properties (fluid losses). The most influential factors affecting the drilling fluid performance, such as the pH, temperature, ionic strength interaction, and pressure, are also debated. Finally, an overview about the simulation at the microscale of fluids flux in porous media is presented, aiming to illustrate the approaches that could be taken to supplement the experimental efforts to research the performance of drilling muds. The information discussed shows that the addition of 2D nanolayered structures to drilling fluids promotes a substantial improvement in the rheological, viscoelastic, and filtration properties, additionally contributing to cuttings removal, and wellbore stability and strengthening. This also offers a unique opportunity to modulate and improve the thermal and lubrication properties of the fluids, which is highly appealing during drilling operations.