This study was conducted at Barangay Villa Cruz, San Mateo, Isabela, from December 2019 to March 2020, to evaluate the growth, yield, and profitability of hybrid rice (SL-8H) under a Modified System of Rice Intensification (SRI) in a lowland irrigated ecosystem. The aim was to evaluate the effect of integrating vermicast with inorganic fertilizers on plant growth, yield, and profitability. A Randomized Complete Block Design with three replications and five treatments was used. The treatments included T1—Conventional/Farmer’s Practice; T2—SRI Protocol (1 ton of vermicast per hectare); T3—Modified SRI1 (120-30-0 kg NPK per hectare); T4—Modified SRI2 (1 ton of vermicast per hectare + 120-30-0 kg NPK per hectare); and T5—Modified SRI3 (0.5 tons of vermicast per hectare + 60-15-0 kg NPK per hectare). The study revealed that Modified SRI1 (T3) produced the tallest plants (108.6 cm), the highest quantity of productive tillers (11.3 hill⁻¹), and the greatest number of full spikelets with (204.9 panicle⁻¹), while the maximum grain yield was achieved in Modified SRI2 (T4) at 10.0 t ha⁻¹, representing a 61% increase compared to that produced under Farmer’s Practice with (6.2 t ha⁻¹). The economic analysis showed that T3 gained the highest return on investment at 131.9%, in contrast to 40.3% for Farmer’s Practice, while no significant differences were noted in 1,000-grain weight and panicle length across the treatments. These results revealed that the integration of SRI principles with balanced organic and inorganic fertilizers notably enhances rice productivity and profitability, which highlights a viable and sustainable substitute for conventional rice farming, providing farmers with enhanced yields and reduced farming expenses.