The tanning industry generates complex effluents with high organic load, salts, sulfides, nitrogen compounds, and chromium; therefore, the evaluation of their treatment should not be limited to physicochemical parameters. In this study, the efficiency of three technologies applied to a previously pretreated composite tannery effluent was compared: ion exchange–adsorption using natural zeolites (T-ZE), electrocoagulation (T-EC), and hydrodynamic cavitation coupled with ozonation (T-HCO). BOD, COD, TSS, ammoniacal nitrogen, sulfides, chlorides, and metals were determined, and toxicity was evaluated through an acute bioassay using Lactuca sativa. Natural zeolite showed the best performance in the removal of COD, TSS, ammoniacal nitrogen, and a high reduction of total chromium; however, its toxicity level was similar to that of the initial sample. Electrocoagulation achieved the highest chromium removal and a high reduction of TSS, but did not produce a significant ecotoxicological improvement. In contrast, hydrodynamic cavitation with ozonation showed the lowest residual toxicity and the highest removal of sulfides and BOD. However, none of the treatments applied individually was able to simultaneously optimize physicochemical quality and effluent detoxification; moreover, all treated samples at 100% concentration maintained marked phytotoxicity. These findings demonstrate that the removal of regulated contaminants does not necessarily translate into a proportional reduction in toxicity and support the need to incorporate bioassays into the selection and scale-up of treatment technologies, as well as to evaluate hybrid treatment approaches.