This clinical resource examines the intersection of Substance Use Disorder (SUD) and Serious Mental Illness (SMI), highlighting how co-occurring conditions significantly amplify the risk of impulsive aggression and violence. It provides a detailed breakdown of DSM-5-TR diagnostic criteria alongside a substance-specific guide to behavioral manifestations during intoxication and withdrawal. Additionally, the document offers structured risk assessment frameworks and evidence-based pharmacological protocols for managing acute agitation safely in complex clinical settings.