Purpose <p>Informal caregivers (ICs) of patients with advanced incurable diseases experience psychological distress, unmet needs, and impaired health-related quality of life (HRQOL). While research on ICs in inpatient palliative care is expanding, less is known about their specific problems, needs, and resources in palliative home care settings.</p> Methods <p>This cross-sectional, single-center study consecutively recruited 76 adult ICs within 72 h of initiating specialist palliative home care. ICs completed standardized questionnaires assessing psychosocial distress, anxiety, depression, importance and fulfilment of needs, HRQOL, social support, and sources of meaning. Descriptive and regression analyses were conducted to explore associations between outcomes.</p> Results <p>The results revealed that 78% of ICs experienced clinically relevant psychosocial distress, with 46% experiencing severe distress. Over one-third of ICs showed signs of anxiety or depressive disorders. HRQOL scores were significantly lower than those of the general population, particularly in mental health and emotional role functioning. About one-third of IC’s needs were unmet, especially regarding emotional support (e.g., feeling hope) and treatment information. Personal relationships and financial security were key sources of meaning, and 77% reported moderate to strong social support. Higher distress, anxiety and depressive symptoms were each significantly associated with lower mental and physical HRQOL.</p> Conclusion <p>ICs in palliative home care experience substantial psychological distress, impaired HRQOL, and unmet needs. To improve their well-being, it is crucial to address emotional and informational needs, enhance social support, and promote sources of meaning. Tailored interventions are essential to support ICs in the setting of palliative home care.</p>