Background: Care bundles, small sets of evidence-based practices implemented together, are widely used to improve safety and outcomes for hospitalized adults. However, bundle components, implementation strategies, and measured outcomes vary across clinical domains. Objective: To synthesize recent evidence on multidisciplinary care bundles (ICU liberation/ABCDEF; ventilator-associated pneumonia [VAP] bundles; central line–associated bloodstream infection [CLABSI] bundles; sepsis bundles; transition of-care bundles), and report their impact on patient-centered outcomes, safety events, and quality metrics. Methods: We conducted a PRISMA-aligned review of nine primary studies (2022–2025) spanning randomized trials, cohort and before–after designs, multicenter surveillance, and system-wide implementations. Outcomes included mortality, mechanical ventilation (MV) duration, ICU/hospital length of stay (LOS), VAP and CLABSI rates, delirium, health-related quality of life (HRQoL), and bundle compliance. Results: ABCDEF bundle programs increased bundle compliance and were associated with reductions in next-day mortality, MV duration, and ICU LOS. VAP bundles reduced VAP incidence and prolonged time-to-VAP in high-compliance groups. A multicenter CLABSI study reported an incidence of =4.2/1000 line-days with moderate bundle adherence; risk increased with prolonged ICU stay and multiple catheters. A transition-of-care bundle improved HRQoL through 180 days. Across studies, implementation success hinged on protocols, multidisciplinary teamwork, data feedback, and education. Conclusions: Multidisciplinary bundles improve meaningful outcomes when delivered with high fidelity and supportive implementation infrastructure. Targeted strategies to boost compliance, especially awakening/breathing trials, early mobility, subglottic suction, and protocolized CVC care, appear pivotal.