Retrieving the spent photocatalysts from the reaction system is always a challenging task. Therefore, the present work is focused on immobilizing sulfur-doped-Bi2O3/MnO2 (S-BOMO) heterojunction photocatalysts over different support matrices and evaluating their performance for the removal of sulfamethoxazole (SMX) in water under visible light. Our findings revealed S-BOMO coated clay beads (S-BOMO CCB) achieving more than 86% (240 min) SMX degradation ∼3, ∼1.3, and ∼2 times higher compared to S-BOMO coated on the different substrates, including glass beads, floating stones, and polymer material substrates, respectively. Mott-Schottky measurements confirmed the construction of the Z-scheme heterojunction involving MnO2 and 2S-Bi2O3. This Z-scheme mechanism, along with its narrow band gap of 1.58 eV, resulted in a rapid spatial transfer of the photogenerated charge carriers between the semiconductors and is believed to enhance the overall photocatalytic activity of the nanocomposite. Radical trapping and electron paramagnetic resonance results clearly established the active role of hydroxyl radicals and hydrogen peroxide in the degradation of SMX. Further, the 2S-BOMO CCB demonstrated excellent stability and photocatalytic activity over multiple runs. According to the sensitivity analysis and the results of anion effect experiments, phosphate and sulfate ions exhibit a significant impact on sulfamethoxazole degradation. Toxicity analysis revealed that 2S-BOMO CCB and sulfamethoxazole degradation byproducts were apparently innocuous. Additionally, the practical applicability of 2S-BOMO CCB was examined in various real water matrices, with the degradation efficiency followed the order: tap water < groundwater < surface water < hospital wastewater < municipal wastewater < pharmaceutical industry wastewater. The economic assessment revealed the reduction in the overall cost of the immobilized 2S-BOMO following the recovery process. Overall, the findings of this work provided critical insights into the synthesis and performance of incredibly effective and stable immobilized photocatalysts for the degradation of pharmaceutical pollutants.