While digital health interventions (DHIs) have become an increasingly common approach to address HIV vulnerability among young sexual and gender minority men who have sex with men (YSGMMSM), few studies consider the role of neighborhood disadvantage in DHI efficacy and engagement. The present study is a secondary data analysis of 212 YSGMMSM aged 16-24 that combined biological and clinical survey data from the primary efficacy randomized controlled trial (RCT) of P3, a PrEP adherence DHI, with a measure of neighborhood disadvantage to characterize P3 engagement and efficacy among high and low disadvantage neighborhoods. We found that participants residing in high disadvantage neighborhoods engaged with P3 a median of 63 days (IQR = 39-76), compared to 77 days (IQR = 51-82) in low disadvantage neighborhoods. Among those who received the P3 intervention, participants residing in high disadvantage neighborhoods had higher odds of PrEP non-adherence (OR = 3.6, CI = 1.2, 10.4). Further, we found that there was minimal difference in PrEP non-adherence rates among those residing high disadvantage neighborhoods between intervention and control groups (28% vs. 25%) compared to 9% in the intervention condition and 18% in the control condition among those residing in low disadvantage neighborhoods. Despite this, receiving the P3 intervention did not moderate the relationship between neighborhood disadvantage and PrEP non-adherence. These findings suggest that neighborhood disadvantage may play a role in PrEP adherence DHI efficacy and engagement among YSGMMSM. Further research is needed to quantify the role of neighborhood disadvantage in YSGMMSM using HIV DHIs.