BACKGROUND: Executive functioning (EF) deficits are troubling for adolescents and young adults (AYAs) after cancer treatment. Physical activity (PA) may enhance neural activity underlying EF among older adults affected by cancer. Establishing whether PA enhances neural activity among AYAs is warranted. As part of a two-arm, mixed-methods pilot randomized controlled trial (RCT), this proof-of-concept sub-study sought to answer the following questions: (1) is it feasible to use neuroimaging with EF tasks to assess neural activity changes following a 12-week PA intervention? And (2) is there preliminary evidence that a 12-week PA intervention enhances neural activity among AYAs after cancer treatment? METHODS: AYAs in the pilot RCT were approached for enrollment into this sub-study. Those who were eligible and enrolled, completed functional magnetic resonance imaging (fMRI) with EF tasks (letter n-back, Go/No Go) pre- and post-PA intervention. Sub-study enrollment, adherence to scheduled fMRI scans, outliers, missing data, and EF task performance data were collected. Data were analyzed with descriptive statistics, blood oxygen level dependent (BOLD) analyses, and paired sample t-tests. RESULTS: Nine eligible participants enrolled into this sub-study; six attended scheduled fMRI scans. One outlier was identified and was subsequently removed from the analytical sample. Participants showed no differences in EF task performance from pre- to post-PA intervention. Increases in neural activity in brain regions responsible for motor control, information encoding and processing, and decision-making were observed post-PA intervention (p < 0.05; n = 5). CONCLUSIONS: Findings  show that fMRI scans during EF tasks detected neural activity changes (as assessed by the BOLD signal) from pre- to post-PA intervention. Results thus suggest future trials confirming that PA enhances neural activity underlying EF are needed, though feasibility issues require careful consideration to ensure trial success. TRIAL REGISTRATION: clinicaltrials.gov, NCT03016728. Registered January 11, 2017, clinicaltrials.gov/ct2/show/NCT03016728.