Purpose: This study aims to evaluate the fatal consequences of the rising methamphetamine (MA) abuse in Eastern Saxony, Germany, and to examine the broader societal impact of MA on the region. Methods: Sociodemographic, forensic toxicological, forensic medical, and psychiatric data from 74 cases of deaths associated with MA were analyzed to identify significant trends and findings (2005–2019). Results: The majority of cases involved male individuals and non-natural deaths, with accidental MA intoxications and suicides being the predominant categories. The Years of Potential Life Lost (YPLL) was calculated at 49.8 years. The majority of natural deaths were related to cardiovascular conditions (e.g. cardiogenic shock, left ventricular hypertrophy (LVH), myocardial infarction), metabolic (e.g. diabetic ketoacidosis, alcohol withdrawal delirium) and inflammatory causes. In cases of fatal MA mono-intoxications and mixed intoxications involving MA, significantly higher MA blood concentrations were observed compared to intoxications primarily caused by other substances. Individuals in socioeconomically precarious situations are especially vulnerable to MA-associated deaths. Conclusion: There has been an increase in MA-related fatalities in Eastern Saxony since 2005. Accidental MA intoxications were the leading cause of death, followed by violent suicides. Challenging living conditions and social circumstances are especially vulnerable to MA-associated deaths. The study underlines the need for a comprehensive, coordinated approach to tackle the MA problem and reduce the number of MA-associated deaths.