The paper proposes a method for guard-band customization to improve the energy efficiency of commercial FPGAs. We deploy custom delay-based sensors alongside any user design to indirectly monitor, in real-time, the functional integrity of the target under voltage scaling. We develop a reliable sensing mechanism and regulate the FPGA operation by holistically considering process, voltage, and temperature variations during run-time. Tests with Xilinx Zynq SoC FPGAs and real benchmarks show significant power savings, in the area of 16–27%, while preserving nominal timing performance for only 1.6% resource overhead.