Progress in technology and industrial developments demands the efficient and successful energy utilization and its management in a greater extent. Conventional heattransfer fluids (HTFs) such as water, ethylene glycol, oils and other fluids are typically low-efficiency heat dissipation fluids. Thermal management is a key factor in diverse applications where these fluids can be used, such as in automotive, microelectronics, energy storage, medical, and nuclear cooling among others. Furthermore, the miniaturization and high efficiency of devices in these fields demand successful heat management and energy-efficient materials. The advent of nanofluids could successfully address the low thermal efficiency of HTFs since nanofluids have shown many interesting properties, and the distinctive features offering extraordinary potential for many applications. Nanofluids are engineered by homogeneously suspending nanostructures with average sizes below 100 nm within conventional fluids. This chapter aims to focus on a detail description of the thermal transport behavior, challenges and implications that involve the development and use of HTFs under the influence of atomistic-scale structures and industrial applications. Multifunctional characteristics of these nanofluids, nanostructures variables and features are discussed in this chapter; the mechanisms that promote these effects on the improvement of nanofluids thermal transport performance and the broad range of current and future applications will be included.