Portal hypertension (PH) is a common clinical syndrome characterized by a pathologic increase in portal venous pressure, its pathophysiological characteristics occurs owing to extensive fibrosis within the liver parenchyma, causing increased vascular resistance and elevated portal pressure. As PH develops, collateral vessel formation and arterial vasodilation progress, enhancing the blood flow to the portal circulation. Increased levels of circulatory vasodilators are believed to be caused by portosystemic shunting and bacterial translocation, leading to the redistribution of the blood volume with central hypovolemia. Hyperdynamic circulatory syndrome promotes the development of esophagogastric varices and splenomegaly. Cirrhosis-induced blood flow obstruction leads to the splenic sinusoidal dilation and congestion, hyperplasia of fibrous tissue, and proliferation of splenic myeloid cells, culminating in hypersplenism. This condition is an important sign of advanced chronic liver disease and PH. Angiogenic factors play a central role in the establishment of collateral circulation and the mechanism of splenic pathological enlargement by regulating angiogenesis. PH hemodynamic abnormalities and associated compensatory pathways represent key targets for targeted therapy. However, the optimization of therapeutic strategies still requires addressing controversies regarding efficacy heterogeneity and long-term safety. This review focuses on our current understanding of the pathophysiological mechanism of collateral circulation and splenomegaly, clinical significance, and novel therapeutic approaches for cirrhosis. Interventions targeting these vascular alterations are expected to exert beneficial effects in managing PH in the future.