Background: Suicide-loss survivors (SLSs) are a population with unique characteristics that place them at increased risk for developing grief complications and painful feelings of guilt that may impact their supportive social environment. However, no studies to date have examined the role of intrapersonal and interpersonal variables that may contribute to prolonged grief symptoms (PGS) as outlined by the new DSM-5 criteria. The present study aimed to extend knowledge regarding the role of interpersonal variables, such as perceived burdensomeness, thwarted belongingness, and self-disclosure, in determining the impact of guilt on the development of PGS among SLSs. Method: This study is part of a longitudinal study, though, in this study, we used a cross-sectional examination of the recently completed fourth measurement. Study participants included 152 SLSs aged 22 to 76 who completed questionnaires measuring guilt, depression, perceived burdensomeness, thwarted belongingness, self-disclosure, and PGS using the Prolonged Grief–Revised Inventory. Participants’ demographics and loss-related characteristics, such as time since suicide and participant’s age at the time of suicide, were examined. Results: Confirming the hypotheses, intrapersonal variables (i.e., guilt and depression), as well as interpersonal variables (i.e., perceived burdensomeness, thwarted belongingness, and self-disclosure), contributed significantly to PGS beyond sociodemographic and loss-related factors. Perceived burdensomeness significantly moderated the contribution of guilt to PGS: for participants with high burdensomeness levels, guilt contributed to PGS more strongly than for participants with low burdensomeness. Conclusion: Guilt is an important contributor to PGS among SLSs, and perceived burdensomeness plays a critical role in moderating this contribution. In light of these findings, it can be suggested that SLSs with high levels of guilt should receive special attention and may benefit from therapeutic interventions focusing on reducing maladaptive cognitions that elicit intense guilt or perceived burden.