The wired charging and the need for battery replacements are critical barriers to unlimited, scalable, and sustainable mobile connectivity, motivating the interest in radio frequency (RF) wireless power transfer (WPT) technology. However, the inherently low end-to-end power transfer efficiency (PTE) and health/safety-related apprehensions about the technology are critical obstacles. Indeed, RF-WPT implementation and operation require efficient and cautious strategies and protocols, especially when targeting high-power charging, which constitutes the scope of this work. Herein, we overview the main factors affecting the end-to-end PTE of RF-WPT systems and their multiplicative effect and interdependencies. Moreover, we discuss key electromagnetic field (EMF) exposure metrics, safety limits, and approaches for efficient and EMF-aware deployment and operation. Quantitatively, we show that near-field RF charging may significantly reduce EMF exposure, and thus must be promoted. We also present our vision of a cyber-physical system for efficient and safe wireless charging, specify key components and their interrelation, and illustrate numerically the PTE attained by two modern low-power multi-antenna architectures in a simple setup. Throughout the paper, we highlight the need for high end-to-end PTE architectures and charging protocols transparently complying with EMF exposure regulations and outline relevant challenges and research directions. This work expands the vision and understanding of modern RF-WPT technology and constitutes a step towards making the technology attractive for worldwide commercial exploitation.