This study critically reviews the use of response surface methodology (RSM) and design of experiments (DOE) in optimizing Fenton and Fenton-like processes for wastewater treatment from 2015 to 2025. Through systematic literature network analysis (SLNA), bibliometric analysis, and systematic review, 78 articles were assessed to address the following research questions. For RQ1, the current landscape is characterized by low collaboration but high productivity in Turkey, Iran, India, and China, where research has shifted from method development toward pilot-scale implementation. The findings for RQ2 identify three influential thematic groups: methodological aspects, advanced oxidation variations, and performance/economic investigations. The ten most-cited publications focus primarily on methodological and applied aspects. For RQ3, researchers have mainly focused on COD/TOC and color reduction in wastewater. However, several issues remain, including insufficient reporting of DOE methodology, limited model validation, restricted factor ranges, and a lack of multi-objective investigations. As suggested guidelines, future studies should consider mandatory DOE methodology reporting, multivariate optimization, multistage pilot-scale validation, and the use of hybrid RSM–ANN/mechanistic modeling approaches.