Spectrophotometry alone is not applicable for the simultaneous determination of drugs in a multi-component pharmaceutical formulation owing to their overlap. In this study, the combination of UV-Vis spectrophotometry and chemometric methods, including continuous wavelet transform (CWT) and partial least squares (PLS) was presented for the simultaneous estimation of tamsulosin (TAM) and solifenacin (SOL) in synthetic mixtures, commercial formulation, and biological sample. The simultaneous spectrophotometric determination of TAM and SOL in binary mixtures, real sample, and biological sample was performed by applying CWT and PLS approaches. In the CWT method, two various wavelet families named Daubechies (db2) at wavelength 223 nm and Biorthogonal (bior1.3) at wavelength 227 nm based on the appropriate zero crossing point were selected for TAM and SOL, respectively. The linear ranges of TAM and SOL were 0.25-4 μg/mL and 10-30 μg/mL, respectively. The limits of detection (LOD) were 0.0459 μg/mL and 0.2085 μg/mL, while the limits of quantitation (LOQ) were 0.3208 μg/mL and 0.6495 μg/mL for TAM and SOL, respectively. The average recovery values of eighteen mixtures were 98.28% and 97.79% for TAM and SOL, respectively. Also, the root mean square error (RMSE) of both components was lower than 2.3. Based on the k-Fold cross-validation in the PLS approach, the optimum number of components related to the TAM and SOL were 9 and 5 with a mean square error prediction (MSEP) of 0.0153 and 0.0370, respectively. The mean recovery values of the test set were found to be 100.09% for TAM and 99.95% for SOL where RMSE values were 0.0064 and 0.0169 for TAM and SOL, respectively. Analysis of variance (ANOVA) was applied to the results of the real sample that there was no significant difference between the proposed methods and the high-performance liquid chromatography (HPLC) as a reference technique. The result obtained revealed that the proposed methods were found to be fast, facile, economical, and precise, which provide a suitable alternative to HPLC technique for the concurrent determination of TAM and SOL in quality control laboratories. UV-Vis spectrophotometry combined with CWT and PLS was developed.Simultaneous analysis of TAM and SOL was performed using the proposed approaches.These methods were implemented on synthetic mixtures, commercial formulation, and biological sample.ANOVA test was used to compare the suggested methods and the HPLC technique.