Objective: Steroid Resistant Nephrotic Syndrome (SRNS) is a rare condition where 10-20% of children with nephrotic syndrome will not respond to prednisolone therapy. Immunosuppressive therapy with drugs such as Cyclosporine A (CsA), Mycophenolate Mofetil (MMF), and Rituximab (RTX) have been often used with varying success. Controversy remains regarding the optimal use and combination of these drugs. This study aimed to describe the characteristics and disease course of SRNS in children treated with combination therapy with CsA, MMF, and/or RTX. Study design: A retrospective single- center chart review including patients with SRNS who were treated at a single tertiary pediatric care center (2008-2020). The study included all children with SRNS treated with at least two immunosuppressive agents (IA), and with a minimal follow-up period of one year to evaluate drug response, IA toxicity and kidney function. Results: The study included 26 children with a mean age of onset of 4.3 ± 2.78 years. Gender-ratio M/F of the study population was 2.25. All patients were treated with a combination of IA, with the most common combination being CsA and MMF. Complete remission was achieved in 34.6% of patients, and the mean time to remission after initiating the second-line IA was 4±1.41 months versus 6.71±3 under CsA (P <10-3). Thus, cumulative remission survival curves showed no significant difference. Toxicity due to immunosuppressive therapy was described in 65.5% of cases, mainly with CsA. Thirteen patients (50%) developed severe (stage 3, 4 or 5) chronic kidney disease (CKD), among whom (n=3; 23%) went to end-stage CKD. The mean time to progression to end-stage CKD was 45 ± 36 months after diagnosis mean estimated glomerular filtration rate was significantly lower compared to the initial rates: 76.40 ± 37.38 versus121.30 ± 33.54 ml/min/1.73m² (P<10-3). Conclusions: Combination therapy with CsA, MMF, and RTX can be an effective treatment option for children with SRNS. However, further studies are needed to determine the most effective and safe combination therapy for this challenging condition. This study provides insights into the use of IA in the management of SRNS.