In the last decade, chemical, biological, radioactive, nuclear, and explosive (CBRN-e) attacks have become severe risks to countries, prompting connected parties to prioritize CBRN-e training. CBRN-e training is typically performed as physical exercises, and although such training is necessary and beneficial, repeating the same training program can be time-consuming and costly. In this study, newly developed versions of two previous serious games—Hospital and Biogarden— and a new mining serious game were developed for training purposes in Virtual Reality (VR), Mixed Reality (MR), and personal computer (PC) environments. The Hospital and Biogarden games’ scenarios were based on the joint activities held in 2018 in France and Belgium as part of the EU H2020 European Network Of CBRN Training CEnters (eNOTICE) project, while the mining game was created over a replica of a training mine at a university in Turkey. Sixteen CBRN-e experts from the eNOTICE project, who took part in the physical training programs in France and Belgium, evaluated the games. For evaluation and extensive feedback, presence, system usability scale, technology acceptance model questionnaires, and open-ended questions were conducted. The findings revealed that serious games have a vast potential in CBRN-e training, and the comparisons of different environments provided invaluable testbeds giving hindsight to develop a future training program.