Synthetic cathinones (SCs) were confirmed as the second most prevalent class of NPS in 2024, underscoring their widespread availability and use. Notably, the SCs seizure and related intoxication cases increased within the European Union, involving mostly 3-chloromethcathinone, 3-methylmethcathinone, 2-methylmethcathinone, and N-ethylnorpentedrone. Italy has observed a distinct trend, with methylendioxy pyrrolidinohexanophenone (MDPHP) emerging as a significant concern. This technical note aims to provide a comparative analysis of the most recent data concerning the emergence and the spread of MDPHP in Italy. Data from the National Early Warning System on Drugs indicate that the total amount of seized MDPHP increased from 2021 to 2024. In 2023, MDPHP-related intoxication cases peaked at 47, considering either alone or in combination with other drugs, followed by a slight decrease in 2024. In Italy, MDPHP seems to dominate the Italian black market of SCs and with two fatalities reported. This increased demand for MDPHP raises health concerns, indicating the necessity to enhance drug-related harm reduction services and improve a multidisciplinary network that provides data for understanding the complex phenomenon of NPS.