Endogenous endophthalmitis (EE) is a rare but potentially sight-threatening disease with an appreciable mortality rate. Diabetes mellitus remains the most frequently associated condition especially in the Asian population, which potentiates Klebsiella pneumoniae involvement. Endogenous Klebsiella pneumoniae endophthalmitis (EKE) usually has a poor final visual outcome despite treatment with intravitreal and systemic antibiotics. We report three cases of EKE with systemic involvement Klebsiella pneumoniae invasive syndrome (KPIS). KPIS was diagnosed in three patients with multiple comorbidities who presented with a blurring of vision and eye redness. Patient 1 was a 63-year-old Malay man diagnosed with left eye panophthalmitis with multifocal liver and prostate abscesses. He underwent drainage of the liver abscess and eventually evisceration of the left eye due to scleral perforation. Patient 2 was a 66-year-old Malay woman diagnosed with left eye endophthalmitis. Due to hemodynamic instability, vitrectomy was delayed and eventually sustained corneal perforation and eviscerated. The patient eventually succumbed to infection. Patient 3 was a 42-year-old Malay woman diagnosed with KPIS, renal abscess, lung abscess, and left endogenous endophthalmitis. She underwent a vitrectomy but her postoperative vision remained poor. All patients received multiple intravitreal antibiotics and systemic antibiotics. KPIS is frequently associated with catastrophic disabilities. Our cases highlight the importance of an early suspicion of systemic involvement in patients presenting with EKE. Prompt diagnosis, emergent radiographic evaluation, early adequate drainage, and appropriate treatment with antibiotics potentially improve survival and visual prognosis.