Background/Objectives: The COVID-19 pandemic accelerated the shift toward community- and home-based care models. Within this transformation, Family and Community Nurses (FCNs) have become key in bridging hospital and primary care, supporting continuity, self-care, and quality of life (QoL). Despite increasing recognition, evidence on FCN-led interventions remains fragmented. This systematic review and meta-analysis aimed to synthesize evidence on the impact of FCN interventions on QoL and clinical outcomes in post-COVID and people living with chronic conditions managed in community and home settings. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Scopus, CINAHL, PsycINFO, Embase, and Cochrane Library (January 2020–November 2024). Eligible studies were randomized controlled trials evaluating FCN-led interventions. Primary outcomes were QoL (measured with validated tools) and glycemic control (HbA1c). Secondary outcomes included hospital readmissions, anxiety, depression, and self-care abilities. Risk of bias was assessed using the Cochrane RoB2 tool for randomized controlled trials. Random-effects meta-analyses were performed, with heterogeneity evaluated by I². The protocol was prospectively registered in PROSPERO (CRD42024567890) before data extraction. Results: Seventy-one studies (n = 19,390) were included. Interventions comprised home visits, telehealth, patient education, and case management. Pooled analyses demonstrated significant improvement in QoL (SMD 0.34, 95% CI 0.18–0.50) and reduction in HbA1c (−0.47%, 95% CI −0.69 to −0.25). FCN interventions also reduced hospital readmissions (RR 0.74, 95% CI 0.62–0.89) and improved mental health outcomes. Most studies were judged at low to moderate risk of bias. Conclusions: FCN-led interventions significantly enhance QoL, mental health, and clinical outcomes while reducing hospital readmissions. These findings highlight the strategic importance of integrating FCNs into community-based healthcare models.