The recent approval of a fixed-dose combination of silodosin (SOD) and solifenacin succinate (SOF) for overactive bladder syndrome has created a need for innovative analytical approaches enabling their simultaneous quantification. In this work, seven novel, eco-friendly, and cost-efficient spectrophotometric methods were developed for the concurrent determination of SOD and SOF. These methods overcome the limitations of conventional techniques by eliminating the need for complex instrumentation, labor-intensive procedures, and large volumes of hazardous organic solvents, offering a sustainable and accessible analytical alternative. A direct UV method (Method I) enabled selective quantification of SOD at 270 nm (1.0–15.0 μg/mL) with complete spectral independence from SOF. Given the substantial overlap between SOD and SOF spectra, six advanced UV-based methods including dual-wavelength, first derivative, ratio spectra difference, first derivative of ratio spectra, ratio subtraction, and absorption factor were innovatively applied for the accurate quantification of SOF (1.0–12.0 μg/mL). The applicability of the proposed methods was demonstrated through accurate analysis of SOD and SOF in combined pharmaceutical formulations and spiked human plasma, with no interference from excipients or endogenous compounds. The proposed methods were designed to be multifunctional, allowing their application in various analytical settings. They were successfully validated and applied for the quality control analysis of co-formulated pharmaceutical tablets, determination of SOD in spiked human plasma for biological use, and for environmental monitoring in different water matrices. This broad applicability highlights the methods’ versatility, robustness, and practical value in routine laboratory analysis. Furthermore, their performance in environmentally relevant aqueous samples underscored their sensitivity and robustness, yielding excellent recovery rates and low %RSD values. Method greenness and practicality were critically evaluated using the GAPI, AGREE, and the recently introduced CACI tool, all confirming the exceptional eco-friendliness and economic viability of the approaches. Full compliance with ICH Q2(R2) guidelines further affirms their validity for routine quality control and environmental monitoring.