Ultrasound-assisted germination (UAG) has been proposed as a process intensification strategy to enhance seed performance while improving resource efficiency. This study combines thermoacoustic multiphysics modeling with controlled experimental validation to evaluate resonance-driven UAG in Cucurbita pepo. Frequency-domain analysis identified 40 kHz as the resonance condition of the seed system, enabling localized acoustic energy concentration. Thermoacoustic simulations demonstrated that temperature increases remained below 46 ◦C across all exposure times, ruling out bulk thermal effects and supporting a predominantly mechanical activation mechanism associated with enhanced permeability and mass transfer. Experimental treatments (40 kHz, 1.5 MPa, 5–25 min) revealed a non-linear germination response to acoustic exposure. A 10 min treatment produced the optimal outcome, increasing final germination from 20% in untreated seeds to 47% and reducing the time required to reach steady state from 13 to 10 days. Longer exposure times did not generate proportional improvements, indicating the presence of a finite acoustic energy window beyond which diminishing returns occur. Because daily water (0.45 L·day−1) and electrical (0.438 kWh·day−1) consumption remained constant across treatments, the shortened germination period directly reduced cumulative resource demand. Under optimal conditions, total water consumption decreased by approximately 1.35 L and electricity use by 1.31 kWh per germination cycle relative to the control. When normalized per percentage point of germination achieved, energy and water intensity were reduced by nearly threefold. The integration of multiphysics modeling with biological experimentation establishes a mechanistically validated and energy-optimized framework for UAG, supporting its application in resource-efficient controlled-environment agricultural systems.