Adolescence and early adulthood are marked by increased exposure to novel situations, frequently accompanied by failure and uncertainty about future success. Decision-making in these contexts is often motivated intrinsically, without explicit promise for future reward. However, little is known about the neural systems that support perseverance in the face of challenge when extrinsic reward is not offered. In this dissertation, a multi-method program of research was employed to investigate the neurobiological contributors to perseverance in a sample of 13- to 30-year-olds (N=99, 61 females). Findings indicate perseverance is associated with differential neural response to the motivational value of information and regulation of neural systems tracking affective signals associated with negative feedback. Of particular import were motivational and value systems located in the striatum and medial prefrontal cortex, salience regions including the insula, and connectivity between the executive control system and fronto-insular regions. This research also identified age-related differences in perseverance decisions and neural functioning during a novel task assessing situational factors associated with motivation. Younger participants were less likely to persevere and demonstrated increased superior frontal gyrus activation to negative feedback, potentially reflecting less clear representation of the motivational value of negative feedback. A developmental shift toward increased valuation of positive feedback compared with monetary reward was also observed, consistent with extant understanding of reward sensitivity during adolescence. Finally, this research demonstrates individual differences in deliberative thinking and inflammation are associated both with perseverance behavior and neural response. Older participants reported more deliberative thinking, which was associated with perseverance and reduced activation in the salience network in response to negative feedback. Among adolescents, perseverance was associated with higher concentrations of the pro-inflammatory cytokine interleukin-6, which was in turn associated with reduced insula activation. These individual difference findings highlight the importance of neural and biological response to feedback as a contributor to perseverance. Intrinsically motivated perseverance is associated with numerous positive benefits and this dissertation makes a substantial contribution to explicating how situational factors contribute to engaging with challenge despite failure.