The present study investigates the oxidative technique of hydrodynamic cavitation (HC) for the treatment of a highly refractive, bulk drug industry effluent with an initial total organic carbon (TOC) content of 69960 mg/l. A qualitative insight into the pharmaceutical industry, drug production, and effluent characteristics is presented. Experiments on the undiluted effluent were conducted in accordance with central composite design (CCD). For the venturi-based HC studies, variation of pH (3.63-10.36), inlet pressure (2.95-13.04 bar), and treatment time (26.36-93.63 min.) were studied, besides investigating their effects on treatment efficiency. HC treatment yielded a maximum 25% reduction in TOC with a cavitational yield of 65.69 × 10-3 mg/J for an optimum combination of pH 7, inlet pressure 8 bar, cavitation number of 0.242, and treatment time 60 minutes (17 recirculations). Furthermore, synergetic effects of increasing inlet pressure and effluent temperature were quantified, and found to effectuate a maximum increase of 1781% in vapour pressure, and decrease of 77% in cavitation number. Lastly, effects of operating factors on treatment efficacy and the success of HC system were summarized. © 2020 Elsevier Ltd.