A stability-indicating high-performance thin layer chromatography (HPTLC) was used to develop and evaluate a method to identify mirabegron (MIRA) and silodosin (SILO) individually and in their combined dosage form. According to literature review, there is no documented HPTLC technique for determining SILO and MIRA simultaneously. As a result, a method was developed to determine the combination of MIRA and SILO. For the HPTLC method, a stationary phase of silica gel 60 F254 HPTLC plates were used. In this investigation, the mobile phase comprised isopropyl alcohol–methanol–triethylamine in the ratio of 6:4:0.1 (V/V). The method was established as per International Council for Harmonisation’s (ICH) requirements. SILO and MIRA had correlation values (R2) of 0.9959 and 0.9978, respectively, for concentration ranges of 0.16–0.48 and 0.5–1.5 µg/band. The percent recovery for SILO and MIRA ranged from 99.36 to 102 and from 99.98 to 102.13, respectively. The percentage relative standard deviation (%RSD) values for MIRA and SILO for interday precision varied from 0.34 to 1.7 and 0.8 to 1.8, respectively. Regarding intraday precision, the %RSD for SILO and MIRA varied between 0.73 and 1.08 and 1.3 to 1.6, respectively. For SILO and MIRA, the limits of detection were found to be 0.04 and 0.09 µg/band, while the limits of quantification were identified as 0.12 and 0.28 µg/band, respectively. A robustness analysis was carried out by intentional alteration in composition of mobile phase and time of saturation, and %RSD for SILO and MIRA stayed within the allowable range. According to the forced degradation studies conducted in acid, base, oxidative, thermal, and photolytic environments, both medications were found to be unstable in every situation. The developed method is accurate, precise and shows stability for the analysis of SILO and MIRA in a combination dose form since it satisfies all ICH requirements.