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Our aim was to better understand the underlying psychiatric, psychosocial, and psychodynamic aspects of mass shootings in the United States (US). The Mother Jones database of 115 mass shootings from 1982-2019 was used to study retrospectively 55 shooters in the US. After developing a psychiatric-assessment questionnaire, psychiatric researchers gathered multiple psychosocial factors and determined diagnoses and treatment by evaluating the clinical evidence obtained by interviewing forensic psychiatrists, who had assessed the assailant, and/or by reviewing psychiatric evaluations conducted during the judicial proceedings. All 35 surviving-assailant cases were selected. Additionally, 20 cases where the assailant died at the time of the shootings were randomly selected from the remaining 80 cases. The majority of assailants (87.5%) had misdiagnosed and incorrectly treated or undiagnosed and untreated psychiatric illness. Most of the assailants also experienced profound estrangement not only from families, friends, and classmates but most importantly from themselves. Being marginalized and interpersonally shunned rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is misdiagnosed or not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with severe psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychotherapeutic and pharmacologic treatments.