(1) Chronic heart failure (CHF) is a typical component of the polymorbid profile of an elderly patient. The aim of this systematic review was to search for data from pharmacokinetic (PK) studies of any drugs in patients with CHF to systematize information on changes in PK parameters depending on the physicochemical properties (PCPs) of the drug and route of its administration. (2) A systematic review of PK studies in patients with CHF was performed using Elibrary.ru, United States National Library of Medicine (PubMed), China National Knowledge Infrastructure (CNKI), and Directory of Open Access Journals (DOAJ). The final number of included articles was 106. A descriptive and correlation analysis of PK data and PCPs of drugs included in the study was carried out. Inclusion criteria: PK study, available PK parameters, demographic data, and diagnosed CHF. Risk of bias was assessed using ROBINS-I. (3) Evaluation of correlations between PCPs of drugs and their PK revealed a link between (i) plasma protein binding (PPB) and volume of distribution for lipophilic drugs; (ii) PCPs, half-life, and clearance for drugs with high PPB; and (iii) PPB and clearance for hydrophilic and amphiphilic drugs. (4) Hypoalbuminemia associated with CHF may lead to an increased volume of distribution of lipophilic drugs; lipophilic drugs used in CHF patients may be associated with prolongation of the half-life period and reduction in clearance; highly protein-bound drugs may manifest with reduced clearance. PK characteristics identified in this review should guide modifications to dosing regimens in CHF patients receiving medications from different groups. © 2025 Elsevier B.V., All rights reserved.