The paper considers the conducted study of the complex effect of low-pressure cold spraying parameters, namely the nozzle inlet temperature, stand-off distance, and powder feed rate on the adhesion and deposition efficiency of coatings from a Ni+Al2O3 powder on VT3-1 titanium alloy substrate. Based on predetermined information, the main levels and intervals of factor variation were selected. The dependence of the adhesion and deposition efficiency on the selected variables was approximated by a second-order polynomial. In accordance with the developed matrix of the experiment (central compositional design), a coating of the studied powder was deposited. The average value of these parameters was determined using standard methods for studying the adhesion strength (ASTM C603) and the deposition efficiency for thermal spray coatings. Based on the results of experimental data, regression equations were obtained for adhesion and deposition efficiency. For the purpose of checking the adequacy of the model, an analysis of variance was performed. It was confirmed that the obtained empirical dependences can be used to predict the adhesion and deposition efficiency of cold spraying of coatings from a Ni+Al2O3 powder on VT3-1 titanium alloy in the specified ranges of values of spraying parameters. Multi-factor optimization of the spraying parameters in order to obtain maximum values of adhesion strength and deposition efficiency was performed using the response surface methodology in the Stat-Ease 360 software. Three-dimensional and contour graphs of the dependence of the adhesion and deposition efficiency on the studied parameters were developed from the obtained empirical models. The optimal combination of parameters of low-pressure cold spraying, which ensures the maximum adhesion (34.78 MPa) and deposition efficiency (29.46%) of the Ni+Al2O3 coating mixture, is the nozzle inlet temperature—537 °C, stand-off distance—11 mm, and powder feed rate—0.6 g s−1.