A novel, eco-friendly spectrofluorimetric method has been developed and validated for the first time for simultaneous determination of tadalafil (TDF) and silodosin (SLD) in pharmaceutical dosage forms and environmental water samples without the need for prior separation. This innovative approach exploits the emission fluorescence of both drugs, employing excitation at 270 nm and emission detection at 328 nm for TDF and 454 nm for SLD. The method demonstrated excellent linearity across the concentration ranges of 50.0–1200.0 ng mL-1 for TDF and 1.0–300.0 ng mL-1 for SLD (r > 0.9999), with remarkable limits of detection of 10.94 ng mL-1 and 0.28 ng mL-1, respectively. The high sensitivity and precision (RSD < 0.70 %), with recovery rates ranging from 99.50 % to 101.00 % in pharmaceuticals and 97.31 % to 102.83 % in environmental water emphasize the method’s robustness and practical applicability for therapeutic drug monitoring and environmental surveillance. Application to content uniformity testing of tablet formulations, in accordance with British Pharmacopoeia guidelines, further demonstrates the method’s versatility. Greenness assessments using the AGREE and complex moGAPI metrics, alongside operational efficiency evaluation through the Click Analytical Chemistry Index (CACI), confirm the method’s sustainability and minimal environmental impact. Fully compliant with ICH Q2(R1) guidelines, this validated protocol offers a pioneering, rapid, and sustainable alternative for routine quality control and environmental monitoring.