This study aimed to identify distinct suicide profiles, associated signs of suicidal intent, and patterns of modifiable risks to inform targeted prevention efforts. Using data from the National Violent Death Reporting System (NVDRS) for 2003-2020, researchers identified five suicide profiles: comorbid mental health and substance use disorders, mental disorders alone, crisis, alcohol-related, and intimate partner problems; physical health problems; and polysubstance use. The largest profile, class 4 (31.7%), predominantly faced physical health challenges and had the lowest rates of disclosing suicidal intent and leaving suicide notes. Adjusted analyses showed that compared to class 1, class 4 had higher odds of not disclosing suicide intent (OR, 2.58) and not leaving a suicide note (OR, 1.45). Class 4 also had the lowest rates of psychiatric illnesses and psychotropic medication use. The study highlights the need for tailored prevention strategies, emphasizing the importance of improving the detection and treatment of coexisting mental health conditions, substance and alcohol use disorders, and physical illnesses. Means restriction strategies are crucial for reducing suicide risks across most profiles, underscoring a multifaceted approach to suicide prevention.This study aimed to identify distinct suicide profiles, associated signs of suicidal intent, and patterns of modifiable risks to inform targeted prevention efforts. Using data from the National Violent Death Reporting System (NVDRS) for 2003-2020, researchers identified five suicide profiles: comorbid mental health and substance use disorders, mental disorders alone, crisis, alcohol-related, and intimate partner problems; physical health problems; and polysubstance use. The largest profile, class 4 (31.7%), predominantly faced physical health challenges and had the lowest rates of disclosing suicidal intent and leaving suicide notes. Adjusted analyses showed that compared to class 1, class 4 had higher odds of not disclosing suicide intent (OR, 2.58) and not leaving a suicide note (OR, 1.45). Class 4 also had the lowest rates of psychiatric illnesses and psychotropic medication use. The study highlights the need for tailored prevention strategies, emphasizing the importance of improving the detection and treatment of coexisting mental health conditions, substance and alcohol use disorders, and physical illnesses. Means restriction strategies are crucial for reducing suicide risks across most profiles, underscoring a multifaceted approach to suicide prevention.