Within an increasingly connected world, the exponential growth in the deployment of Internet of Things (IoT) applications presents a significant challenge in power and data transfer optimisation. Currently, the maximization of Radio Frequency (RF) system power gain depends on the design of efficient, commercial chips, and on the integration of these chips by using complex RF simulations to verify bespoke configurations. However, even if a standard 50Ω transmitter’s chip has an efficiency of 90%, the overall power efficiency of the RF system can be reduced by 10% if coupled with a standard antenna of 72Ω. Hence, it is necessary for scalable IoT networks to have optimal RF system design for every transceiver: for example, impedance mismatching between a transmitter’s antenna and chip leads to a significant reduction of the corresponding RF system’s overall power efficiency. This work presents a versatile design framework, based on well-known theoretical methods (i.e., transducer gain, power wave approach, transmission line theory), for the optimal design in terms of power delivered to a load of a typical RF system, which consists of an antenna, a matching network, a load (e.g., integrated circuit) and transmission lines which connect all these parts. The aim of this design framework is not only to reduce the computational effort needed for the design and prototyping of power efficient RF systems, but also to increase the accuracy of the analysis, based on the explanatory analysis within our design framework. Simulated and measured results verify the accuracy of this proposed design framework over a 0–4 GHz spectrum. Finally, a case study based on the design of an RF system for Bluetooth applications demonstrates the benefits of this RF design framework.