Irritability, a common presenting complaint in youths, is a transdiagnostic symptom present in multiple forms of psychopathology and linked with aberrant reward processing. Childhood adversity elevates the risk of psychopathology and is also associated with anomalies in reward processing. While previous studies have examined the relationship between childhood adversity (abuse vs. neglect), irritability, and reward processing separately, it remains unclear how they all interact. Thus, we aim to investigate the relative and interactive effects among these variables. During fMRI acquisition, 45 adolescents (25 females; mean age=14.91, SD=1.89) completed a child-friendly monetary incentive delay task, a paradigm measuring neural reward processing where they hit or missed the target with or without expecting a reward. Childhood Trauma Questionnaire assessed childhood abuse and neglect experiences; Affective Reactivity Index assessed irritability symptoms. Whole brain ANCOVAs evaluated neural patterns associated with reward anticipation and feedback in relation to childhood abuse, neglect, and irritability symptoms. Whole-brain-corrected group-level analyses demonstrated significant Abuse X Irritability X Reward Condition (reward vs. no-reward) X Performance (hit vs. miss) interactions in prefrontal cortices (controlling for neglect, ps<.05), associated with reward and emotion processing. Among youths whose irritability was low, youths with high abuse showed greater activation to hit vs. miss in the reward condition and miss vs. hit in the no-reward condition, whereas youths with low abuse showed the opposite pattern, indicating a moderating role of childhood abuse; among youths whose irritability was high, such brain activation differences were attenuated, suggesting the presence of irritability diminishes any moderating role of abuse. Interestingly, the differences in activation across conditions were greater when the target was missed, suggesting reward omission may be both an irritability and “threat” probe, and thus more salient. Additionally, for youths with both high irritability and high abuse, there was little difference in neural response across conditions, representing a qualitatively different neural activity pattern. Taken together, our findings suggest that youths with different combinations of irritability symptoms and childhood abuse may have varying profiles of neural reward processing, emphasizing the need for individualized treatment approaches for youths with different symptomatology and histories of abuse.