Adults with heart failure (HF) suffer from a high prevalence of depressive and anxiety symptoms, and therapies available to treat these symptoms have varying effectiveness. Data on the factors contributing to this needs-services gap (i.e., complexity) remain limited. This dissertation aimed to examine factors related to this complexity in adults with HF and specifically focuses on 1) psychological resilience and its association with depressive symptoms, 2) inflammation and its association with depressive and anxiety symptoms, and 3) the association between depressive and anxiety symptoms and polypharmacy, measured using a daily drug count. For the first manuscript of this dissertation, the study aims were achieved using the methods of a systematic review. The two remaining manuscripts are data-based, leveraging data from an existing repository of HF datasets collected between 2001 and 2009. The findings of the systematic review (Chapter 2) suggest that psychological resilience is negatively associated with depressive symptoms in adults with cardiac disease (n=10 of 13 studies). Using logistic regression (Chapter 3), inflammation measured by standardized c-reactive protein was found to be associated with increased odds of worsened depressive symptoms over three months (OR=1.75, p=0.042) in adults with HF (n=120). The final data-based manuscript (Chapter 4) used multivariable linear regression to examine the association between depressive and anxiety symptoms and polypharmacy (measured using a daily drug count) in adults with HF (n=299). However, anxiety was found to have no significant association with polypharmacy (p>0.05), while depression, social support, left ventricular ejection fraction, race, biological sex, and multimorbidity were significantly associated (all ps<0.05). The findings of this dissertation support the development of mechanism-based interventions to address depressive and anxiety symptoms in HF. The results also support previous findings of race- and sex-based disparities in polypharmacy.