Bipolar disorder is a complex psychiatric illness that is characterized by alternating episodes of mania and depression that significantly affect the quality of life. It is a chronic condition that has multifactorial pathophysiological mechanisms that remain incompletely understood, and therapeutic outcomes often fail to achieve long-term remission. This review visits the changing landscape of the development of bipolar disorder, in particular, the contributions of metabolic dysfunction and diabetes, which are increasingly acknowledged as important contributors to disease onset, progression, and treatment resistance. The review also explores current advancements, both pharmacological and non-pharmacological advancements for the management of the disease. By integrating the insights from several biological domains, the need for a broader and personalized treatment paradigm that goes beyond neurotransmitter theories is highlighted for improving patient outcomes.