The paper presents a comprehensive analysis of new data for drilling and seismic survey of the oil and gas potential of deep-seated Paleozoic horizons of the Caspian Basin in Kazakhstan. The features of the development and occurrence of large Paleozoic uplifts and sedimentary strata promising for prospecting are specified. A set of geological and geophysical methods was applied, and magnetic and gravitational anomalies of potential fields were analyzed in the southern, southeastern, and eastern marginal parts of the southeastern sector of the Caspian Basin. This is supplemented with new data obtained by a set of reconnaissance methods, and the section attributed to the Paleozoic at depths up to 5.5–8.0 km and its Devonian–Lower Carboniferous sequence are specified. New data were obtained on the area of distribution and occurrence of Upper Devonian and Lower Carboniferous sediments, geological conditions and prerequisites were revealed that refined the trace of the pre-Devonian complex and of the Lower–Middle Devonian sediments. Analysis of the distribution of large local prospecting objects has confirmed the presence and development of megauplifts, which are zones of hypsometrically elevated Devonian–Lower Carboniferous sediments. In the contour of the megauplift, structural elements have developed that are less significant, but promising in terms of hydrocarbon content. Based on the results of studying and refining the distribution patterns of large Devonian?Lower Carboniferous objects and identifying megauplifts, it is possible to optimize regional studies in the Caspian Basin for the period of 2020–2030.