Abstract Background and Aims Prognostic models that identify individuals with chronic kidney disease (CKD) at highest risk of developing kidney failure help clinicians to make decisions and deliver precision medicine. People with CKD are very likely to have multiple long-term health conditions (multimorbidity) and often experience frailty. These factors impact progression of kidney disease and influence the risk of other outcomes such as death. It is unclear to what extent prognostic models, that estimate the risk of kidney failure, consider the impact of multimorbidity and frailty and whether these models are valid in such sub-populations. This systematic review (CRD42022347295) describes and evaluates the representation of multimorbidity and frailty within cohorts used to develop and/or validate prognostic models assessing the risk of kidney failure in individuals with CKD. The review aims to determine if multimorbidity or frailty has been considered in relation to prediction of kidney failure and if reliable prognostic models exist for use in this population. Method We included studies that described the derivation, validation or update of a kidney failure prognostic model (outcome assessed at ≥2 years) for use in adults with CKD and reported at least one measure of either discrimination or calibration. The primary outcome for the review was the representation of multimorbidity or frailty in these models. An electronic search for published peer-reviewed articles involved MEDLINE, CINAHL Plus and the Cochrane Library – CENTRAL and was supplemented with manual review of references from previous systematic reviews and clinical guidelines. Results A total of 97 studies, reporting 121 different kidney failure prognostic models were identified. A total of 2 925 413 participants and 149 380 kidney failure events were included across all studies. Included participants had a mean age of 58.9 years (SD 9.6), 44.4% were female, with a mean eGFR of 47.5 ml/min/1.73 m2 (SD 10.7). Only two studies reported multimorbidity, measured by Elixhauser Comorbidity Index and Charlson Co-morbidity Index (CCI), and a single study reported a self-reported proxy frailty measure. The rates of specific co-morbidities were reported in a greater proportion of studies: 67.0% (n = 65) studies reported baseline data on diabetes, 54.6% (n = 53) reported hypertension, and 39.2% (n = 38) reported cardiovascular disease. No studies included frailty in model development and only one study considered multimorbidity as a predictor variable (via CCI). No studies assessed model performance in populations with multimorbidity. A single study assessed clinical utility of a model and referral algorithms considering frailty and the risk of kidney failure and death. Conclusion There is a paucity of kidney failure risk prediction models that consider the impact of multimorbidity and/or frailty in adults with CKD, resulting in a lack of clear evidence-based practice and guidance for multimorbid or frail individuals. These knowledge gaps should be explored to help clinicians know whether these models can be used for patients who experience multimorbidity and/or frailty.