Myocardial infarction with non-obstructive coronary arteries (MINOCA) in end-stage kidney disease (ESRD) patients represents a critical clinical challenge, situated at the confluence of diagnostic ambiguity and therapeutic uncertainty. MINOCA, accounting for 3–15% of all acute myocardial infarctions (AMI), carries a significant burden of morbidity and mortality comparable to obstructive MI, especially in patients with comorbidities. The prevalence of renal dysfunction among MINOCA patients is notably high, impacting short- and long-term outcomes. ESRD patients face an exceptionally elevated risk of AMI and significantly higher mortality rates, often presenting with atypical symptoms and chronically elevated troponin levels, which complicates MINOCA diagnosis and may lead to underestimation. The pathophysiology of MINOCA in ESRD is complex, involving chronic microvascular dysfunction, systemic inflammation, uremic toxins, and a prothrombotic state, all exacerbated by hemodynamic fluctuations during dialysis. Diagnostic challenges include interpreting non-specific ECG changes, elevated troponins, and the risks associated with contrast media during angiography, CCTA, IVUS/OCT, and CMR. While CMR is pivotal for etiological clarification, its use in ESRD requires careful consideration of gadolinium agents. Management is highly individualized, with initial standard MI therapies (antiplatelets, statins, beta-blockers, ACE inhibitors/ARBs) recommended, followed by adjustments based on the identified mechanism. However, the optimal duration and intensity of antiplatelet therapy remain uncertain due to increased bleeding risk in ESRD. A multidisciplinary approach is essential to coordinate dialysis with cardiac interventions, minimizing contrast exposure and hemodynamic stress. Prognostically, MINOCA patients with renal impairment experience significantly worse outcomes, with high cardiovascular and non-cardiovascular mortality. Future research requires dedicated randomized trials to define optimal therapeutic strategies, including dual antiplatelet drug therapy duration, intensive statin use, and anti-inflammatory therapies. Developing specific risk scores and optimizing dialysis regimens are also crucial steps toward improving outcomes in this vulnerable patient population.