In the early postpartum period, dairy cows undergo significant adaptations in Ca and lipid metabolism, immune function, and inflammatory processes. Concurrent exposure to endotoxins from the uterus, gastrointestinal tract, or mammary gland increases the risk of disease and reproductive problems. Metabolic and inflammatory imbalances during this phase can have both immediate and long-term effects on reproductive health. Associations between metabolic disorders and reproductive outcomes are often confounded by immune activation and systemic inflammation. However, optimal markers, thresholds, and durations for identifying maladaptation and predicting adverse health or reproductive outcomes remain unclear. This narrative review examines key physiological changes during the transition period, including hypocalcemia, lipid mobilization, immune activation, systemic inflammation, and uterine disease. We discuss how these events may affect the dominant follicle, corpus luteum, oocyte, and uterus, potentially leading to prolonged anovulation, reduced estrus expression, impaired response to synchronization protocols, lower progesterone concentrations, and compromised fertility. Understanding these mechanisms will support the development of strategies to monitor, prevent, and mitigate the impacts of transition-related maladaptation on reproductive performance. Such advancements can enhance the health and fertility of high-producing dairy cows.