This study delves into the development and optimization of photocatalysts, namely ZnO NPs/Zeolite and TiO2 NPs/Zeolite, for the degradation of two beta-blocker drugs, including Atenolol (AT) and Metoprolol (ME). Structural and morphological analyses of the catalysts were conducted, and optimal conditions for drug degradation were determined using a Box-Behnken design. The results underscored the significant influence of pH, catalyst amount, drug concentration, and H2O2 concentration on the degradation process using ZnO NPs/Zeolite and TiO2 NPs/Zeolite as the catalysts. The optimal values of drug concentration, pH, catalyst amount, and H2O2 concentration, were determined to be 32 and 33 mg L−1, 4.2 and 4.6, 428 and 386 mg, and 2.6 and 2.5 mM utilizing ZnO NPs/Zeolite and TiO2 NPs/Zeolite as the catalyst, respectively. Following optimization, the kinetics of the photodegradation process were investigated, revealing promising rates and half-life times for both drugs. The pseudo-first-order rate constants for Atenolol and Metoprolol degradation were 0.064 ± 0.007 min−1 and 0.065 ± 0.004 min−1 with ZnO NPs/Zeolite and 0.071 ± 0.007 min−1 and 0.071 ± 0.006 min−1 with TiO2 NPs/Zeolite, respectively. Furthermore, ZnO NPs/Zeolite and TiO2 NPs/Zeolite demonstrated reusability up to 5 and 6 times, respectively, without significant activity loss. The comparative analysis highlighted the superior performance of TiO2 NPs/Zeolite over ZnO NPs/Zeolite, attributed to lower consumption, shorter degradation time, improved reusability, and compatibility with milder acidic conditions. Overall, the research showcases the potential of ZnO NPs/Zeolite and TiO2 NPs/Zeolite as an effective and sustainable solution for removing Metoprolol and Atenolol contaminants.